Venereology Question and Answers

Description of Primary Skin Lesions

Question 1. Define primary And Secondary skin lesions and give examples.
Answer:

 

Read And Learn More: General Medicine Questions and Answers

Papulosquamous Disorders

Psoriasis

Question 2. Discuss the types and describe the various modalities of treatment of psoriasis including topical, systemic, drugs, and phototherapy.
Answer:

It is a non-infectious, chronic papulosquamous, T-cell-mediated inflammatory skin disorder and is one of the most common skin diseases. It usually follows a relapsing and remitting course.

• Psoriasis Gender: It equally affects males and females.
• Psoriasis Age: It occurs in two peaks of age.
  • Early onset (age 16–22) is more common and often has a positive family history. It has an increased prevalence of the human leukocyte antigen (HLA) group Cw6.
  • Late-onset (peaks at age 55–60 years) has no HLA association.

Psoriasis Etiology

The exact etiology of psoriasis is not known.

• Psoriasis Genetic factors: The genetic component is complex and polygenic. There is a clear genetic predisposition (with a positive family history in >50% of patients) in association with certain environmental triggers. Nine susceptibility genes have been identified (PSORS1 to PSORS9), the most important being PSORS1.
• Psoriasis Environmental factors: Several environmental triggers produce psoriasis in a genetically predisposed individual. These include infections, stress, physical injury, trauma, smoking, alcohol, and drugs.

Psoriasis Pathogenesis

• Psoriasis results from interactions of genetic and environmental factors. There is a shortened cell cycle time for keratinocytes (36 hours compared with 311 hours in normal skin) and a decreased turnover time of the epidermis (4 days from basal cell layer to stratum corneum, compared with 27 days in normal skin).
• Available evidence suggests that cells in genetically susceptible individuals, triggering factors activate the antigen-presenting cells (dendritic/Langerhans), which in turn activate CD4+ TH1 and TH17 cells via interleukin (IL)-12 and
• IL-23, respectively and these T cells enter the skin and accumulate in the epidermis. These T cells secrete mediators [tumor necrosis factor (TNF)-α and interferon-γ by TH1; IL-17A, 17F and 22 by TH17], which activate keratinocytes to produce antimicrobial peptides (Example: β-defensins), cytokines (Example: TNF-α, IL-1β, and IL-6) and chemokines.

Psoriasis Pathology

• Increased epidermal cell proliferation (hyperproliferation of keratinocytes): Proliferation of the subepidermal
  vasculature leads to dilated, tortuous blood vessels within the dermal papillae surrounded by a mixed neutrophilic and lymphohistiocytic perivascular infiltrate.
• Dense inflammatory cell infiltrates. Polymorphonuclear abscesses may be seen within mildly spongiotic foci of the superficial epidermis (spongiform pustules) and within the parakeratotic stratum corneum (Munro’s microabscesses).

Psoriasis Clinical Features

• Psoriasis can involve the skin, scalp, and nails and can present with different clinical patterns.
• Clinically, skin lesions are characterized by well-defined pink-red, sharply demarcated macules, papules, or rounded plaques that are usually covered by silvery scales with a whitish halo around lesions (Woronoff’s sign).
• It predominantly affects extensor surfaces and scalp, and has a chronic fluctuating course. There is an increased association of psoriasis with HIV infection.
• Grattage test: Scales in a psoriatic plaque can be accentuated by grating with a glass slide.
• Auspitsign: Three steps
  • Step 1: Gently scrape the lesion with a glass slide—this accentuates the silvery scales (Grattage test positive). Scrape off all the scales
  • Step 2: Continue to scrape the lesion—a glistening white adherent membrane (Burkley’s membrane) appears
  • Step 3: On removing the membrane, punctate bleeding points become visible—positive Auspitsign.

Psoriasis Types of Psoriasis

• Plaque psoriasis (psoriasis vulgaris), chronic plaque psoriasis
• Guttate psoriasis (small raindrop-like psoriatic lesions)
• Inverse psoriasis (flexural psoriasis)
• Localized pustular psoriasis
• Generalized pustular psoriasis
• Palmoplantar psoriasis
• Erythrodermic psoriasis
• Von Zumbusch psoriasis (pustular + erythroderma)

Psoriasis Plaque Psoriasis (Psoriasis Vulgaris), Chronic Plaque Psoriasis

• It is the most common form and accounts for 90% of cases.
• Lesions:
  • Symmetrically distributed plaques involving the scalp, extensor surfaces of the elbows, knees, gluteal cleft, lower back, ears, and back. Plaques 1–10 cm in diameter with raised, well-defined margins
  • Thick silvery scales are frequently present (although bathing may remove scale)
  • Classically asymptomatic, although some patients report pruritus, irritation, or pain
  • Pitting of nail plates and involvement of intertriginous areas (umbilicus and intergluteal cleft) may occur.
  • Psoriatic lesions can be induced in susceptible individuals by minor local injury/trauma, a process known as the Koebner phenomenon.
• Exacerbating factors: Drugs (lithium, β-blockers, chloroquine, NSAIDs, ACE inhibitors, and terbinafine), infections (bacterial and viral), and ethanol abuse.

Psoriasis Associated Features of Psoriasis

• Nails: Involvement is common and may be observed
  up to 50% of patients with psoriasis.
• These include
• “Thimble pitting” of the nail plate,
• Distal separation of the nail plate from the nail bed (onycholysis),
• Yellow-brown discoloration underneath the nail plate (“oil drop” sign),
• Subungual hyperkeratosis, and
• Thickening of the nail (onychodystrophy).
• For diagnosis of nail involvement: More than six nails should be involved with each nail having >20 pits.
• Psoriatic arthropathy: It may be seen in 5–10% of psoriatic patients. It usually develops several years after the appearance of skin lesions and most of these will have nail changes. It is a form of chronic seronegative spondyloarthropathy.
• Others: It may be associated with comorbidities such as ulcerative colitis, Crohn’s disease, coronary artery disease, metabolic syndrome, and lymphoma.

Psoriasis Investigations and Diagnosis

In most cases, the diagnosis can be made based on the history and physical examination alone. A biopsy is seldom necessary.

Psoriasis Management of psoriasis

Treatment depends on the type, location, and extent of the disease.

Psoriasis General management

• Education, explanation, reassurance, and instructions are important.
• Instructed to avoid excess drying or irritation of the skin and to maintain adequate hydration of the skin

Psoriasis Treatment can be divided into four broad categories namely

• topical agents,
• ultraviolet (UV) therapies,
• systemic agents, and
• biological therapies.

Psoriasis Treatment of psoriasis vulgaris: A three-step approach.

Step 1: Topical treatments

• Emollients/moisturizers: Petroleum jelly and thick creams, especially effective when applied after hydrating bath or shower
• Topical corticosteroids: These are a mainstay for treatment. Moderate to high potency ointments (Example: betamethasone 0.5%) ± occlusion by tape or plastic wrap are recommended for thick plaques on extensor surfaces, whereas low-potency ointments (Example: 0.05% fluocinonide) are usually sufficient for face and intertriginous areas.
• Coal tar: Usually used in conjunction with steroids, although can be used alone
• Calcipotriene and Calcitriol: Vitamin D3 analog that affects the growth and differentiation of keratinocytes
• Tazarotene: Topical retinoid (vitamin A derivative)
• Topical calcineurin inhibitors: Topical tacrolimus and pimecrolimus
• Salicylic acid: Keratolytic that softens and removes scale from plaques, allowing topical meds to penetrate
• Topical anthralin

Question 3. Discuss PUVA (psoralen and ultraviolet A) therapy in psoriasis.
Answer:

• Step 2: Phototherapy: Effect likely through immunomodulatory properties
• Sunlight: Careful sun exposure may improve psoriasis, but sunburn may exacerbate it.
• UVB (295–320 nm) radiation: Erythema-inducing doses (3–5×/week until remission) are used for moderate to extensive disease, alone or in combination with topical tar.
• UVB narrow band (311 nm): It has been shown to be more effective than the broader band in some studies, inducing more apoptosis of T-cells.
• Psoralen and ultraviolet A: Photochemotherapy with oral psoralen (8-methoxy psoralen) followed by exposure to UVA (320–400 nm) radiation is used for moderate-to-severe disease when UVB fails.
• It is effective (75% of patients note marked improvement), but increases the risk for cataracts, pigmentation, premature skin aging, and skin cancer. Psoralens are natural photosensitizers found in many plants.
• Psoralen molecules intercalate between the two strands of DNA and on excitation with ultraviolet A (UVA), photons cross-link the DNA strands.
• It is thus a pro-drug, which after oral administration is distributed throughout the body, but only activated in skin that is exposed to UVA.
• Other uses of PUVA include vitiligo, mycosis fungoides, atopic dermatitis, and senile pruritus. The risk of skin cancer and folate deficiency is associated with PUVA therapy.
• High-energy 308-nm excimer laser: It treats only involved skin and allows higher doses to be delivered to the plaques, compared with traditional phototherapy.
• Two regimens used commonly are:

1. Goeckerman regimen: UVB + coal tar
2. Ingram regimen: Coal tar + UVB + dithranol

Step 3: Systemic therapy

• Methotrexate: It is effective in severe psoriasis, psoriatic arthritis, and psoriatic nail disease.
• Acitretin: Vitamin A analog used for the treatment of severe psoriasis, especially pustular and erythrodermic variants. It is a teratogen and pregnancy is contraindicated for 3 years after discontinuing the drug. It may be used in combination with UVB or PUVA.
• Cyclosporine: T-cell suppressor indicated for severe psoriasis not responsive to other agents
• Apremilast, a phosphodiesterase 4 inhibitor, is indicated for the treatment of moderate-to-severe plaque psoriasis.

Biologics, immunomodulatory drugs

• Etanercept: Recombinant TNF-alpha inhibitor, approved for treatment of psoriatic arthritis and for adults with moderate-to-severe plaque psoriasis
• Alefacept: Recombinant protein that binds to CD2 receptor on T-lymphocytes
• Efalizumab: It is a monoclonal antibody to CD11a. It is approved for moderate-to-severe plaque psoriasis
• Infliximab: TNF-alpha inhibitor
• Human interleukin-12/23 monoclonal antibody:
• Ustekinumab, a fully human monoclonal antibody against the p40 subunit of IL-12 and IL-23, is effective.
• Guselkumab is a human immunoglobulin G1 (IgG1) lambda monoclonal antibody that binds to the p19 subunit of IL-23.
• Monoclonal antibody against the p40 molecule shared by IL-12 and IL-23: For example, canakinumab is effective in moderate and severe psoriasis.
• Risankizumab is a humanized monoclonal antibody directed against the p19 subunit of IL-23 and IL-39.
• Brodalumab (an anti-IL-17 receptor antibody) and ixekizumab (an anti-IL-17 monoclonal antibody) can also be effective in psoriasis.
• Newer treatment options:
• Climatotherapy (bathing in seawater in combination with sun exposure)
• Balneophototherapy (salt water baths with artificial UV exposure)

Lichen Planus

Question 4. Describe the clinical features and treatment modalities for lichen planus.
Answer:

Lichen planus is a pruritic inflammatory dermatosis that is commonly associated with mucosal involvement. It may affect the skin (cutaneous lichen planus), oral cavity (oral lichen planus), genitalia (penile or vulvar lichen planus), scalp (lichen planopilaris), nails, or esophagus.

Lichen Planus Etiology

Autoimmune: An autoimmune mechanism is suspected because of its association with hepatitis C, inflammatory bowel disease, primary biliary cirrhosis, autoimmune hepatitis, hepatitis B, alopecia areata, myasthenia gravis, and thymoma. There are similarities with graft-versus-host disease (GVHD).

Drugs, such as thiazides, INH, allopurinol, angiotensin-converting enzyme (ACE) inhibitors, and antimalarials, can produce lichenoid eruptions.

Lichen Planus Clinical Features

Lichen Planus Age and gender: Lichen planus affects women more than men (at a ratio of 3:2) and occurs most often in middle-aged adults.

Lichen Planus Characteristics of Lesion

Lichen Planus Skin lesions:

• The typical rash of lichen planus is well described by the “5 P’s”: Well-defined pruritic, planar, purple, polygonal papules, or plaques.
• Sites involved: Flexor surfaces especially wrists, flanks, medial thighs, shins of tibia, glans penis, nails, scalp, and oral mucosa.
• There may be a characteristic fine lacy white pattern (network) on the surface of lesions (Wickham’s striae).
• Koebner’s phenomenon is observed.
• After lesions subside, post-lichen hyperpigmentation occurs.
• Mucous membrane: Involvement is common (30–70%) and the prominent symptom is of severe pain rather than itch. The
  mouth is the most commonly affected. It can also affect genital and other mucosal surfaces.
• Nail involvement: Occurs in about 10% and causes a thinning of the nail with longitudinal ridges and may progress to complete loss of the nail plate (pterygium formation).
• Scalp involvement: Lichen planopilaris is the specific name given to lichen planus on the scalp that may cause permanent, scarring alopecia.

Lichen Planus Diagnosis

Lichen Planus Histological changes:

Characteristic histological changes include

1. hyperkeratosis with thickening of the granular cell layer,
2. basal cell degeneration, and
3. dense, band-like T-lymphocyte infiltrate at the dermal–epidermal junction, with an affinity for the epidermis (epidermotropism).
4. The dermo-epidermal junction becomes ragged and appears “saw-toothed”. The basal layer shows liquefactive degeneration with colloid (apoptotic) bodies, Colloid or Civatte bodies in the upper dermis.

Lichen Planus Prognosis

It is usually self-limiting and often clears by 18 months but can recur at intervals.

Lichen Planus Complications of Lichen Planus

• Complications of lichen planus (LP).
• Squamous cell carcinoma in oral ulcerative lesions
• Cicatricial alopecia in scalp LP
• Postinflammatory hyperpigmentation

Lichen Planus Management

• Treatment is symptomatic.
• Topical corticosteroids: Potent local corticosteroids (Example: 0.05% clobetasol propionate, 0.1% triamcinolone ointment, twice daily for 2–4 weeks) are helpful in patients with limited disease.
• Oral lesions may require high-potency steroids given as an ointment, gel, or mouthwash. Topical 0.1% tacrolimus ointment or pimecrolimus may be very useful for painful oral disease unresponsive to steroids.
• Oral therapy: Short courses of systemic corticosteroids (oral prednisolone 30 mg daily for 2–4 weeks) are sometimes required for extensive disease.
• Widespread lichen planus may require UVB, PUVA, or UVA1 and in resistant cases, retinoids or immunosuppressants such as azathioprine and ciclosporin may be helpful.
• Hydroxychloroquine and dapsone have also been tried.

Acanthosis Nigricans

Question 5. Write a short note on acanthosis nigricans (AN).
Answer:

It is a skin lesion marked by thickened, verrucous (warty) hyperpigmentation of the skin with a velvety texture (Fig. 22.8) predominantly of the flexural areas (axillae, skin folds of the neck, groin, and anogenital regions) including the lips.

• In 80% of cases, it is associated with benign conditions [most commonly with obesity, insulin resistance, and diabetes, and drugs such as nicotinic acid, fusidic acid, stilbestrol, oral contraceptive pills (OCPs)] and develops gradually, usually during childhood or puberty.
• They are associated with very high levels of insulin owing to insulin resistance. Obesity-associated AN is sometimes termed “pseudoacanthosis nigricans”.
• In the remaining cases, it arises in association with underlying cancers (most commonly gastrointestinal adenocarcinomas), usually in middle-aged and older individuals.
• In this setting, it occurs as a paraneoplastic phenomenon caused by growth factors released from tumors. Other tumors producing this are Wilm’s tumor and malignant tumors of the bronchus, pancreas, ovary, bile duct, gallbladder, breast, and thyroid.

Associated thickening of palms with accentuated dermatoglyphics is called Tripe palms. Acrochordons (skin tags) may be present.

Acanthosis Nigricans Treatment

• Treat any underlying disease/malignancy.
• Weight loss is advised in the obese.
• Topical or oral retinoids (0.5 mg/kg per day) may be helpful.

Few may benefit from metformin, oral isotretinoin, topical retinoic acid, topical salicylic acid, and oral fish oil

Eczema

Question 6. Describe the etiopathogenesis of eczema. Classify and grade eczema.
(or)Question. Enumerate the drugs used in the treatment of eczema.
Answer:

• Eczema is catarrhal inflammation of sensitive skin, synonymous with the term dermatitis. Eczema is not a specific disease entity and may develop as a final common response of the skin to several causes. These causes may be either exogenous or endogenous in origin.
• It presents a spectrum of clinical presentations from acute to chronic. The acute type is histologically characterized by spongiosis (intercellular edema of the epidermis) and intraepidermal vesiculation (producing multilocular blisters). Chronic eczema shows more epidermal thickening (acanthosis).

Classification of Eczema

Atopic Dermatitis

Question 7. Write a short essay/answer on atopic dermatitis.
Answer:

Atopic dermatitis (AD) is an endogenous type of eczema that develops in individuals who are “atopic” and is the cutaneous expression of the atopic state. The atopic state is characterized by a family history of asthma, allergic rhinitis, or eczema.

Atopic Dermatitis Etiology

The exact pathophysiology is partially defined in atopic dermatitis.

• Genetic factors: Atopic eczema is a genetically complex familial disease and is often associated with positive family history of atopic disease (90% concordance in monozygotic twins but only 20% in dizygotic twins).
• Environmental allergens: Atopy is characterized by generalized and prolonged hypersensitivity to common environmental antigens (For example pollen, food, animal hair, and house dust mite). Atopic individuals develop one or more of a group of diseases such as asthma, hay fever, food and other allergies, and atopic eczema.
• Epidermal barrier impairment: It is a major and perhaps primary factor in atopic eczema. It was observed in Caucasian individuals that loss of function mutations in the epidermal barrier protein filaggrin can predispose to atopic eczema. Filaggrin is coded by the FLG gene on chromosome 1q21.
• Exacerbating factors: Factors that can exacerbate eczema include
• Infection: Infection in the skin or systemic infection can exacerbate atopic eczema. Paradoxically, lack of infection (in infancy) may allow eczema to develop (“hygiene hypothesis”).
• Irritants: Such as strong detergents, chemicals, and woolen clothes
• Severe anxiety or stress in some individuals
• Others: Cat and dog fur, food allergens, dairy products, or eggs

Atopic Dermatitis Clinical features

Atopic Dermatitis Age: Atopic eczema is most commonly seen among young children. About 50% are present within the 1st year of life, and 80% are present by 5 years of age.

Atopic Dermatitis Character of a lesion

• Primary lesions include erythematous macules, papules, and vesicles, which can coalesce to form patches and plaques. The most common presentation is extremely itchy erythematous scaly patches accompanied by scratching.
• The symptom of the itch is so central in the pathogenesis that atopic dermatitis is described as “the itch that rashes and not the rash that itches”.
• It may also present as widespread cutaneous dryness (roughness).
• Acute lesions can produce small vesicles. In severe cases, secondary lesions from infection or excoriation (due to scratching) may be marked by weeping and crusting.
• In chronic lesions, repeated rubbing produces lichenification.

Atopic Dermatitis Distribution of lesion: Varies with age

• Lesions are usually found in the periorbital area and the flexor areas such as in front of the elbows and ankles, behind the knees (popliteal fossae), and around the neck.
• In infants, eczema usually starts on the face before spreading to the body.

Atopic Dermatitis Cutaneous and vascular stigmata of atopic dermatitis 

Atopic Dermatitis Diagnosis: It is made based on

1. morphologic features,
2. the distribution of the lesions, and
3. a family and personal history of atopy. About 80% of patients may have high serum IgE levels or high specific IgE levels to certain ingested or inhaled antigens and blood eosinophilia. Hanifin and Rajka criteria are used for diagnosis.

Atopic Dermatitis Complications of Atopic Eczema

Complications of atopic eczema.

Atopic Dermatitis Secondary infection

• Bacterial: Staphylococcus aureus is the most common
• Viral: For example, viral warts and Molluscum contagiosum, especially if treated with topical corticosteroids. Herpes simplex virus (HSV) can cause severe widespread eruption (eczema herpeticum).

Atopic Dermatitis Increased susceptibility to irritants due to defective barrier function Increased susceptibility to allergy:

• Food allergy mainly in infants, For Example., egg, cow’s milk, protein, fish, and wheat may cause an urticarial eruption.

Atopic Dermatitis Management

General measures:

Atopic Dermatitis Atopic eczema

• Education, explanation, and reassurance
• Avoidance of contact with skin irritants (especially soaps or furry animals), heat, and dryness. Advised to wear cotton clothes
• Emollients for moisturizing: Emollients are used to moisturize, lubricate, protect, and soften skin

Atopic Dermatitis Topical anti-inflammatory agents:

• Topical corticosteroid ointments: They should be used judiciously. Depending on the potency, topical corticosteroids can be divided into five groups. Mid-potency topical glucocorticosteroids are used in most treatment regimens.
• Topical immunomodulators: These include two macrolide immunosuppressants namely tacrolimus ointment (0.1% for 3–4 weeks), and pimecrolimus cream (1% for 3–4 weeks). The “triple” combination of topical steroids, emollients, bath oil and soap substitute (Example: aqueous cream) is usually helpful.

Atopic Dermatitis Adjunct therapies:

• Oral antihistamines: Control of pruritus is most often achieved by the use of antihistamines. These include fexofenadine, 180 mg every morning, and hydroxyzine hydrochloride 10–25 mg at nighttime.
• Bandaging: Paste bandaging may be used for lichenified eczema of the limbs. It helps the absorption of topical treatment and also acts as a barrier to prevent scratching.
• Prompt treatment of secondary infection by antibiotics: Secondary infection of eczema may lead to exacerbation of
  should be identified by culture and treated with appropriate systemic antibiotics.

Atopic Dermatitis Phototherapy:

• Narrow-band-UVB phototherapy: Ultraviolet radiation (UVR) treatment—most commonly narrow-band ultraviolet B is used.
• Psoralen and ultraviolet A (PUVA)

Atopic Dermatitis Systemic therapy:

• Systemic glucocorticosteroids should be given for severe exacerbations that do not respond to topical therapy. Generally, oral prednisolone is given in a dose of 0.5–1 mg/kg/day.
• Use of cyclosporin: Cyclosporin is an immunosuppressant that inhibits production of interleukin-2 by T lymphocytes.

Atopic Dermatitis Contact Dermatitis

Atopic Dermatitis Allergic Contact Eczema

This develops as a manifestation of a delayed hypersensitivity reaction following contact with antigens or haptens. Many agents can cause allergic contact eczema and common agents include nickel in costume jewelry and buckles (Example: eczema of the earlobes and umbilicus), chromate in cement (eczema of the hands and foot), and latex in surgical rubber gloves (eczema of the hands and wrist). Allergy persists indefinitely and eczema develops at sites of contact with allergen.

During the acute phase, lesions show edema, erythema, and vesicle formation. Later, vesicles rupture producing oozing, and papules and plaques appear. In the chronic phase, scaling, lichenification, and excoriations predominate.

Atopic Dermatitis Irritant Contact Eczema

This type of eczema can occur in any individual and the injury is due to an inherent characteristic of compound-irritant contact dermatitis. It usually develops on the hands after repeated exposures to irritants (For example: detergents, soaps or bleach, alkalis, and acids) and is common in housewives, cleaners, hairdressers, mechanics, and nurses.

The lesions may be acute (wet and edematous) with strong irritants or chronic (dry, thickened, and scaly) with weak irritants.

Dermatology Venereology and Leprosy Chronic contact dermatitis.

Treatment of contact dermatitis

• Identify and avoid contact with causative agents/irritants and use protective gloves or clothing. In extreme cases, even changing occupations or hobbies may be needed.
• Treatment with high-potency topical glucocorticoids
• In cases where systemic therapy is indicated, daily oral prednisone begins at 1 mg/kg, but usually 60 mg/day is given. It should be tapered over 2–3 weeks.

Atopic Dermatitis Seborrheic Dermatitis

Seborrheic dermatitis is a common, chronic disorder, characterized by red scaly patches or plaques.

Atopic Dermatitis Etiology: It is due to Pityrosporum ovale (also called Malassezia furfur in its hyphal form).

Sites of involvement: Seborrheic dermatitis affects body sites rich in sebaceous glands.

• Scalp: It most commonly affects the scalp (recognized as severe dandruff).
• Facial region: On the face, it affects the nasolabial folds, eyebrows, eyelids, and glabella. Scaling of the external auditory canal and the postauricular areas often show maceration and tenderness.
• Other sites include the central chest, axilla, groin, submammary folds, and gluteal cleft.

Atopic Dermatitis Clinical features: Three age groups are affected by seborrheic dermatitis.

1. In neonates: It presents as yellowish thick crusts on the scalp (cradle cap), face, or groin. Normally, it improves spontaneously after a few weeks.
2. In young adults (especially males): The rash is more persistent and presents as an erythematous scaling along the sides of the nose, in the eyebrows, around the eyes, and in the scalp (dandruff).
3. It is more common in patients with Parkinson’s disease, in those who have had cerebrovascular accidents, and in those with HIV infection (especially with CD4 cell count <400/mm3).
4. In elderly people: It can be more severe and progress to involve large areas of the body.

Atopic Dermatitis Treatment of seborrheic dermatitis:

Treatment is suppressive rather than curative.

• A combination of low-potency topical glucocorticoids (Example: 1% hydrocortisone applied twice daily) with a topical antifungal cream (Example: miconazole or ketoconazole or Ciclopirox olamine cream applied twice daily) is often effective. Topical 0.1% tacrolimus ointment or pimecrolimus cream can also be effective.
• Antipityrosporal agents, such as ketoconazole shampoo and Arachis oil, are useful for the scalp and beard areas. Emollients and a soap substitute may be used as adjuncts.
• High-potency topical glucocorticoids (betamethasone or clobetasol) are effective in cases with severe scalp involvement. However, they should not be used on the face because they may be associated with steroid-induced rosacea or atrophy

Pityriasis Versicolor (Tinea Versicolor)

Question 8. Write short essay/note on pityriasis versicolor (tinea versicolor).
Answer:

• Pityriasis Versicolor is a relatively common persistent, superficial skin condition caused by a common commensal lipophilic yeast—Malassezia furfur (also known as pityrosporum ovale). The yeast is a normal inhabitant of the skin.
• Predisposing factor: Infection is more frequent in warmer, humid climates, and is usually more severe and persistent in immunocompromised individuals.
• The appearance of skin lesion: Typical lesion is round, scaly, oval macules on the upper trunk. It is usually hypopigmented (on dark skin) but occasionally hyperpigmented (on light skin).
• Hypopigmentation is more obvious after sun exposure and tanning. Sometimes, it may have raised erythematous margins. Inappropriate use of topical steroids causes the spread of the lesion.
• Sites affected are upper back, shoulders, and chest but it also affects upper arms, neck, and rarely on the face. The lesions are more extensive in patients in the tropics.
• Other diseases associated with tinea versicolor: Cushing’s syndrome, hyperhidrosis, and altered immune status (Example: HIV).

Pityriasis Versicolor (Tinea Versicolor) Diagnosis

The diagnosis can be confirmed by:

• Skin scraping: It shows a characteristic “spaghetti and meatballs” appearance.
• Wood’s light examination: It shows some pigment (yellow fluorescence) in skin regions involved by tinea versicolor whereas in vitiligo, there is total loss of pigment in the affected areas.

Pityriasis Versicolor (Tinea Versicolor) Treatment

Pityriasis Versicolor (Tinea Versicolor) Topical antifungals

• Selenium sulfide or 2% ketoconazole shampoo to be applied to the affected areas of the body and removed after 30–60 minutes and repeated daily for 1 week. In resistant cases, overnight application may be useful.
• Topical imidazole (miconazole, clotrimazole, and ketoconazole) cream twice daily for 10 days

Pityriasis Versicolor (Tinea Versicolor) Oral antifungals

• Oral itraconazole (100 mg twice daily for 1 week) is given in resistant cases. The pigmentation takes months to recover even after successful treatment.
• Others include ketoconazole (200 mg daily for 10 days or 400 mg/day for 2 days, though less effective), and fluconazole (150–300 mg weekly for 2–4 weeks). The condition may recur but can be retreated.

Pityriasis Versicolor (Tinea Versicolor) Blistering (Bullous) Disorders Of Skin

Blistering skin diseases (BSDs) are skin conditions characterized by blister formation. A blister is an accumulation of fluid between cells of the epidermis or upper dermis. Causes of blister formation
may be genetic, physical, inflammatory, immunologic, and as a reaction to drugs. Blistering disorders are mostly due to autoimmune mechanisms.

Pityriasis Versicolor (Tinea Versicolor) Types of Blistering Diseases

Types of blistering diseases.

Pityriasis Versicolor (Tinea Versicolor) Genetic blistering diseases:

1. Epidermolysis bullosa and
2. Hailey–Hailey
3. disease (benign familial pemphigus)

Pityriasis Versicolor (Tinea Versicolor) Immunobullous diseases:

1. Intraepidermal immunobullous diseases:
2. Pemphigus vulgaris (PV),
3. pemphigus vegetans,
4. pemphigus foliaceus,
5. pemphigus erythematosus, and
6. paraneoplastic PV

Pityriasis Versicolor (Tinea Versicolor) Subepidermal immunobullous diseases:

1. Bullous pemphigoid,
2. pemphigoid gestationis,
3. linear IgA disease,
4. epidermolysis bullosa acquisita, and
5. dermatitis herpetiformis

Pemphigus Vulgaris

Question 9. Write a short essay/note on the etiology, clinical features, diagnosis, and treatment of pemphigus vulgaris.
Answer:

Pemphigus vulgaris (PV) is a potentially fatal mucocutaneous blistering disease.

Pemphigus Vulgaris Etiology

• Autoimmunity: It is thought to be an autoimmune disorder. Patients with PV have IgG4 autoantibodies directed against desmosomal protein desmoglein-1 and -3 (belong to the cadherin family of calcium-dependent adhesion molecules).
• Desmoglein-1 and -3 are expressed in skin and mucosal surfaces. IgG4 autoantibodies are responsible for blister formation and their titer correlates with disease activity.
• Drug-induced pemphigus: Pemphigus may also be drug induced (Example: sulfonamides, penicillins, and antiepileptic drugs).

Pemphigus Vulgaris Clinical features

• Age and gender: It predominates in patients between the fourth and sixth decades of life and both sexes are affected equally.
• Lesions: They typically begin on mucosal surfaces and often progress to involve the skin. Lesions consist of fragile, flaccid blisters that rupture to produce erosions in mucous membranes and skin.

Pemphigus Vulgaris Oral cavity

• Characteristic of lesion: Mucosal involvement (especially oral ulceration) is the most common (up to 75% of cases) presenting sign. Lesions consist of fragile, flaccid blisters that rupture to produce erosions in mucous membranes.
• Sites: Lesions within the oral cavity can be seen anywhere and are most often found in areas subjected to friction trauma (For example cheek mucosa, tongue, palate, and lower lip).

Pemphigus Vulgaris Skin lesions

• Sites: Typically involves the scalp, face, neck, trunk, and intertriginous areas (axilla and groin).
• Skin lesions follow oral lesions and appear as non-itchy flaccid blisters filled with clear fluid that arises on normal skin. Blistering usually becomes widespread and is fragile. They rapidly denude/rupture giving rise to painful erythematous and weeping erosions. Erosions are often large. Intact blisters may be sparse.

Question 10. Write a short essay/note on Nikolsky’s sign.
Answer:

Nikolsky’s sign: It is positive. It is elicited by applying gentle manual sliding pressure to the affected skin (Example: where a blister is located, or rub sideways over the perilesional skin or normal skin with a cotton swab or finger).

• A positive response is indicated by the extension of the blister and/or separation of the epidermis in the area immediately and is known as Nikolsky’s sign.
• This sign is not specific to pemphigus but is also seen in toxic epidermal necrolysis (TEN), StevensJohnson syndrome, staphylococcal-scalded skin syndrome, bullous impetigo, and epidermolysis bullosa. This sign is usually negative in bullous pemphigoid.

Nikolsky’s sign Bulla-spread phenomenon: Gentle pressure on an intact bulla forces the fluid to spread under the skin away from the site of pressure (also called Asboe–Hansen sign, or the “indirect Nikolsky” or “Nikolsky II” sign).

Nikolsky’s sign Diagnosis

• Skin biopsy: Microscopically, it shows a suprabasal blister due to suprabasal (immediately above the basal cell layer) acantholysis (the dissolution or lysis of the intercellular bridges that connect squamous epithelial cells). Acantholytic cells separate from one another, lose their polyhedral shape and appear round (tombstone appearance).
• Direct immunofluorescence: Lesions show a characteristic net-like pattern of intercellular IgG deposits. IgG is
  usually seen at all levels of the epithelium.

Bullous Pemphigoid

Question 11. Write a short essay/note on:
Bullous pemphigoid or pemphigoid
Etiology, clinical features, diagnosis, and treatment of bullous pemphigoid.
Answer:

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease. Mucosal involvement is rare.

Bullous Pemphigoid Age and Gender: It occurs in the elderly in the fifth to seventh decades, with an average age of onset of 65 years. Males and females are equally affected.

Bullous Pemphigoid Etiopathogenesis

• Bullous pemphigoid is caused by autoantibodies against specialized proteins that are involved in the adherence of basal keratinocytes to the basement membrane.
• These linking proteins are called hemidesmosomes and the so-called bullous pemphigoid antigens (BPAGs) are components of these hemidesmosomes.

Bullous Pemphigoid Clinical features

Bullous Pemphigoid Bullae: The patient usually presents with large tense bullae anywhere on the skin but often involves flexor surfaces of the arms and legs, axilla, groin, and abdomen. The bullae may be centered on erythematous or urticated skin. The bullae may contain hemorrhagic fluid.

Pemphigoid can be very itchy. Mucosal ulceration is uncommon and when seen, it is of minor clinical significance. Nontraumatized bullae usually heal without scarring.

Bullous Pemphigoid Diagnosis

Bullous Pemphigoid Skin biopsy: Biopsies of skin lesions show subepidermal blisters with an eosinophil-rich inflammatory infiltrate at sites of vesicle formation and in perivascular areas.

Bullous Pemphigoid Direct immunofluorescence: It shows linear deposits of IgG and C3 at the dermo-epidermal junction.

Bullous Pemphigoid Treatment

• Patients with local or mild disease can sometimes be controlled with the application of very potent topical steroids to all sites in frail elderly patients. Occasionally, it can be controlled by oral dapsone or high-dose oral minocycline, or tetracyclines.
• The mainstay of treatment is systemic glucocorticoid (oral prednisolone 30–60 mg daily). Patients with more extensive lesions respond to systemic glucocorticoids either alone or in combination with immunosuppressive agents. Immunosuppressive agents include azathioprine, mycophenolate mofetil, or cyclophosphamide.

Intravenous immunoglobulin as a steroid-sparing therapy in BP may also be useful.

Dermatitis Herpetiformis

Question 12. Write a short note on dermatitis herpetiformis.
Answer:

• It is characterized by intensely itchy, chronic papulovesicular eruptions distributed symmetrically on extensor surfaces.
• Age: It may start at any age. Most commonly, it occurs in the 2nd, 3rd, and 4th decades of life.
• Skin biopsy: If a vesicle can be biopsied before it is scratched away, the microscopic examination shows a subepidermal blister, with dermal papillary collections of neutrophils (microabscesses).
• DIF (direct immunofluorescence): Granular IgA deposits in normal-appearing skin are diagnostic for DH.
• Most DH patients (not all) have an associated gluten-sensitive enteropathy. So, associated anti endomysial antibodies are positive.

Reactive Disorders Of Skin

Erythema Multiforme

Question 13. Write a short essay/note on precipitating causes, clinical manifestations, and management of erythema multiforme.
Answer:

• Erythema multiforme (EM) is an uncommon acute, self-limiting, recurrent cutaneous and/or mucocutaneous blistering eruption that occurs in individuals of any age.
• Eruptions are characterized by target-shaped plaques commonly over the extremities and the face.

Erythema Multiforme Causes

Erythema multiforme can be triggered by a variety of factors.

1. Infections:

• Viral, Example: herpes simplex, Orf, infectious mononucleosis, hepatitis B, and HIV
• Mycoplasma and other bacterial infections (Example: typhoid)
• Fungal, Example: histoplasmosis and coccidioidomycosis
• Rickettsia

2. Exposure to drugs:

For example, sulfonamides, penicillins, barbiturates salicylates, hydantoins, antimalarials, and carbamazepine

3. Systemic disease:

• Sarcoidosis
• Malignancy (carcinomas and lymphomas)
• Collagen vascular diseases [Systemic lupus erythematosus (Rowell’s syndrome), Wegener’s granulomatosis, dermatomyositis, and polyarteritis nodosa

4. Other: Radiotherapy, pregnancy

Erythema Multiforme Pathogenesis

Immune-mediated disease: It is characterized by keratinocyte injury caused by CD8+ cytotoxic T lymphocytes in the skin. The CD8+ cytotoxic T cells are found in the central portion of the lesions, and CD4+ helper T cells and Langerhans cells are found in the peripheral portions. The epidermal antigens causing the disease are not known.

Erythema Multiforme Classification

Classification of erythema multiforme (EM).

• Em Minor: Cutaneous without mucous involvement
• Em Major (EMM): Cutaneous + mucous involvement
• Mucosal Em: Fuch’s ectodermosis pluriorificialis
• Haem: Herpes-associated EM
• Mpaem: Mycoplasma-associated

Erythema Multiforme Clinical Features of Erythema Multiforme

• Male:Female = 3:2
• Occurs in the young/adolescents
• About 50% of patients give a history of preceding herpetic infection.
• Associated with HLA DQB1  0301 Allele

Erythema Multiforme Elementary skin lesions

Multiforme: As the name implies, it presents with a diverse array of lesions (multiform), including macules, papules, vesicles, and bullae.

Erythema Multiforme Distribution of skin lesions (topography)

• Lesions are symmetrical, acral, and centripetal in distribution
• Extensor aspect: Extremities > face > neck > trunk
• The predilection to sun-exposed areas/Koebnerization present.

Characteristic lesion

Question 14. Write a short essay/note on target lesions, iris lesions, and bull’s eye lesions of erythema multiforme.
Answer:

• Classic target lesion: It consists of three concentric distinct zones/ rings of different colors a dark central circular dusky red (darker red) zone is surrounded by an intermediate light rim (white), which in turn is encircled by an outermost red zone (iris lesions). The central circular zone may show bulla formation or crust. The lesion may resemble a “bull’s eye”.
• Larger lesions show central bulla and marginal ring of vesicles: Herpes iris of Bateman.

Characteristic lesion Mucosal lesions

Mucosal (oral mucosa) involvement is usually absent and, when present, lesions are few in number and mildly symptomatic.

Stevens-Johnson Syndrome

Question 15. Write a short essay/note on Stevens–Johnson syndrome.
Answer:

• Stevens–Johnson syndrome (SJS) is a rare, acute, and life-threatening mucocutaneous disease with systemic involvement and is nearly always drug-related.
• SJS is a “minor form of TEN” with <10% body surface area (BSA) detachment
• Overlapping Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN): Detachment of 10–30% BSA
• Toxic epidermal necrolysis (TEN): Detachment of >30% BSA

Clinical features of Stevens–Johnson syndrome are listed.

Mortality rate in SJS: 1–5%

Toxic Epidermal Necrolysis (Lyell’s Syndrome)

Question 16. Write a short essay/note on toxic epidermal necrolysis.
Answer:

• Toxic epidermal necrolysis is characterized by diffuse necrosis and sloughing of skin and mucosal epithelial surfaces. It begins with severe mucosal erosions and progresses to diffuse, generalized detachment of the skin epidermis.
• Nikolsky sign is often positive, i.e., sliding pressure from a finger on a normal-looking epidermis dislodges the epidermis.
• No target lesions seen
• The mortality rate in TEN: High (30%)

Toxic Epidermal Necrolysis (Lyell’s Syndrome) Management

Toxic Epidermal Necrolysis (Lyell’s Syndrome) Treatment of Erythema Multiforme

• Management of the precipitating factors/causes. If a drug is suspected, it must be discontinued and precipitating infection should be treated.
• Treatment of EM otherwise is nonspecific.
• Severe cases may require systemic corticosteroids.
• Oral acyclovir early reduces the number and duration of lesions.
• Chronic antiviral treatment with acyclovir (400 mg twice daily for 6 months) in herpes-associated outbreaks in patients with recurrent erythema multiforme

Toxic Epidermal Necrolysis (Lyell’s Syndrome) Treatment of SJS (Stevens-Johnson syndrome) and TEN (toxic epidermal necrolysis)

• Maintain the fluid and electrolyte balance
• Manage oral mucosal lesions with mouthwashes. Topical anesthetics may reduce pain and allow the patient to take in fluids
• The area of denuded skin should be covered with compresses of saline
• Systemic corticosteroid is contraindicated in Stevens-Johnson syndrome
• Treatment of toxic epidermal necrolysis is very difficult, but intravenous immune globulin (2–3 g/kg over a period of 2–5 days) may improve the prognosis.

Dress Syndrome

Question 17. Write a short note on DRESS syndrome.
Answer:

Dress Syndrome “Drug reaction with eosinophilia and systemic symptoms”

It is a potentially life-threatening drug-induced, hypersensitivity reaction that includes skin eruption, hematologic abnormalities, lymphadenopathy, and internal organ damage.

Etiology and Risk Factors

Dress Syndrome Clinical Features

Dress Syndrome Systemic symptoms:

• 2–6 weeks after the initiation of the offending drug
• Fever (38–40°)
• Malaise
• Lymphadenopathy: Tender and slightly enlarged. Biopsy shows features of viral lymphadenopathy or benign lymphoid hyperplasia.

Dress Syndrome Visceral involvement: At least one organ is involved in 90% of patients

• Liver: Hepatomegaly, jaundice, and asymptomatic hepatitis
• Kidney: Acute interstitial nephritis
• Lung: Nonspecific symptoms (cough, fever, and tachypnea/dyspnea). CXR/CT—evidence of interstitial pneumonitis and/ or pleural effusion
• Cardiac: Eosinophilic myocarditis and pericarditis
• Gastrointestinal tract (GIT): Diarrhea, mucosal erosions, bleeding, and pancreatitis
• Thyroid: Autoimmune thyroiditis
• Nervous system: Encephalitis, meningitis, and polyneuritis
• Myositis and increase in CPK
• Eye: Uveitis
• It rarely has been associated with shock/multiorgan failure and DIC.

Dress Syndrome Skin:

• Starts as a morbilliform eruption and progresses rapidly to a diffuse/confluent erythema with follicular accentuation
• DRESS is likely when the eruption involves >50% of BSA and/or includes two or more facial edema/infiltrated lesions/ scaling and purpura. The percentage of BSA involved is a marker of disease severity.
• In 20–30%, erythema can progress to exfoliative dermatitis.
• The face, upper part of the trunk, and extremities are involved initially.
• Facial edema in 50% of cases. It is symmetric, persistent, and associated with erythema.
• Mucosa: Inflamed, usually at one site only, does not progress to erosions.

Dress Syndrome Management

Dress Syndrome Drug withdrawal and avoidance of introducing new medications during the course

• Fluid, electrolyte, and nutritional support
• Warm, humid environment, and skincare with warm baths/wet dressings and emollients
• Patients without evidence of renal/pulmonary involvement and only modest elevation of liver transaminases (<3 times) can be treated symptomatically.

For pruritus and skin inflammation, high-potency topical steroids (betamethasone, clobetasol, fluocinonide, clobetasol) are applied 2 times/day for 1 week.

• Patients with severe organ involvement:
  • Acute hepatitis: Withdrawal of offending drug and follow-up by serial LFT. Liver transplant in cases of acute liver failure.

Moderate-to-high dose of systemic corticosteroids in severe lung involvement b(dyspnea, abnormal CXR, and hypoxemia) and severe renal involvement (creatinine >150% basal level, proteinuria, or hematuria).

Given till clinical improvement or normalization of laboratories and then tapered over 8–12 weeks.

Cyclosporine: Second-line therapy for those who do not respond to steroids or if steroids are contraindicated.

Pigmentary Disorders Of Skin

Hypopigmentation

Question 18. List the differential diagnosis of hypopigmented cutaneous lesions/hypopigmentation.
Answer:

Hypopigmentation Causes of Hypopigmentation

Causes of hypopigmentation and/or depigmentation.

Hypopigmentation Genetic

• Albinism
• Piebaldism
• Phenylketonuria
• Waardenburg’s
• syndrome
• Chediak-Higashi
• syndrome
• Tuberous sclerosis

Hypopigmentation Endocrine

Hypopituitarism

Hypopigmentation Chemical

Contact with substituted phenols (in the rubber industry) Chloroquine and h y d r o x y c h l o r o

Hypopigmentation Postinflammatory

• Eczema
• Pityriasis alba
• Psoriasis
• Sarcoidosis
• Lupus erythematosus
• Lichen sclerosis et atrophicus
• Cryotherapy

Hypopigmentation Infections

• Leprosy
• Pityriasis versicolor
• Syphilis, yaws, and pinta

Hypopigmentation Tumors

• Halo nevus
• Malignant melanoma

Hypopigmentation Miscellaneous

• Vitiligo
• Idiopathic guttate hypomelanosis

Question 19. Write short notes on the etiology, clinical features, and treatment of vitiligo.
Answer:

Vitiligo is a common, slowly progressive acquired condition caused by focal loss of melanocytes within the skin resulting in the development of well-circumscribed patches of hypopigmentation.

Treatment of vitiligo Classification

Classification of vitiligo.

Treatment of vitiligo Localized

• Focal vitiligo: One or more macules in one area not clearly in a segment
• Segmental vitiligo: Number of macules in the unilateral segment of the body (stops abruptly at midline)
• Mucosal vitiligo: Affects lips, oral cavity, and genitalia

Treatment of vitiligo Generalized

• Acrofacial vitiligo: Lesions on the acral (hand and feet) and face (perioral)
• Vitiligo vulgaris: Multiple macules bilaterally symmetrically scattered
• Lip–tip vitiligo: Tips of digits and lips only
• Mixed: Any combination of the above
• Universal vitiligo: Complete or near complete depigmentation of the body

Treatment of vitiligo Clinical Features

Treatment of vitiligo Non segmental vitiligo (NSV)

• It presents as a small, depigmented macule that may enlarge and coalesce into larger patches.
• NSV is further divided into subtypes based on the distribution of skin lesions (i.e., generalized, acral, or acrofacial, mucosal, localized, universal, and mixed pattern).
• It is often symmetrical and occurs mainly around body orifices (around the eyes, nose, lips, and genitalia), hands, feet, flexor surfaces of the wrists, ankles, elbows, knees, and major body folds.
• The hair of the scalp, beard, eyebrows, and lashes (leukotrichia) may also show depigmentation.
• Vitiligo fulminant/galloping vitiligo: Rapid downhill course with rapid progression of skin lesions
• Patients are very susceptible to sunburn.
• Nonsegmental vitiligo can spread by the Koebner phenomenon (Fig. 22.17C). Other skin conditions that spread by the Koebner phenomenon include psoriasis, molluscum contagiosum, warts, EM, and lichen planus.

Treatment of vitiligo Segmental vitiligo

It is restricted to one part of the body. The patches of depigmentation are sharply defined. Spotty perifollicular pigment may be seen within the depigmentation.

Sensation in the depigmented patches is normal (unlike in tuberculoid leprosy). Wood’s light examination shows the contrast between pigmented and non-pigmented skin.

Treatment of vitiligo Trichrome vitiligo (vitiligo graduate): Presence of tan-colored zone in-between normal skin and the depigmented macule. Sometimes, a fourth color dark brown is present at sites of perifollicular repigmentation quadrichrome vitiligo.

Treatment of vitiligo Association of vitiligo with other diseases

Vitiligo is associated with other diseases.

• Autoimmune thyroiditis
• Addison’s disease
• Pernicious anemia
• Diabetes mellitus
• Vogt–Koyanagi–Harada syndrome: Vitiligo, poliosis, uveitis, alopecia, meningismus, and hearing difficulties
• Alezzandrini syndrome: Unilateral facial vitiligo, unilateral retinal degeneration, poliosis, and hearing loss
• Kabuki syndrome: Developmental delay, facial dysmorphism, skeletal and visceral anomalies

Treatment of vitiligo Management

• Protect the patches from excessive sun exposure with clothing or sunscreen to avoid sunburn.
• Treatment: Often unsatisfactory

Treatment of vitiligo Topical treatment

It includes the use of potent topical corticosteroids and topical immunomodulators (For example calcineurin-inhibitors tacrolimus 0.1% ointment especially on the face).

Treatment of vitiligo Phototherapy

• Topical psoralen plus ultraviolet-A (UV-A) phototherapy (PUVA therapy) is the most effective pigmentary treatment available for nonsegmental generalized vitiligo.
• Narrow-band UVB (NB-UVB) phototherapy: It is the treatment of choice for active, generalized vitiligo. Cosmetic results are better and side effects are less than PUVA.
• Topical application of corticosteroids along with UVA exposure is often effective.
• Autologous melanocyte transfer is effective for treating stable, focal vitiligo.
• Extensive vitiligo may be treated with the removal of pigment from the remaining normally pigmented skin by using bleaching creams (Example: monobenzylether of hydroquinone and 4-methoxy-phenol).
• Human placental extract and calcipotriol have been tried.
• Systemic treatment
• Surgical treatment

Treatment of vitiligo Pityriasis Alba

• Common skin disorder in children that is usually evident before puberty.
• Cause: Not known, however, there is often a history of atopy.

Treatment of vitiligo Clinical Features

Hypopigmented patches or macules with slight scale, mainly on the face and less frequently on the neck, trunk, and extremities. No permanent damage to the skin. Often improves after puberty.

Treatment of vitiligo Treatment: Use of lubricants and mild topical steroids

Inherited Hypopigmentation Disorders

Question 20. Write a short note on inherited hypopigmentation disorders.
Answer:

• Albinism
• An autosomal recessive inherited disorder
• A genetic defect in melanin synthesis and normal melanocyte number and structure
• Mutation in the tyrosinase gene
• Affected individuals will be born with white hair and skin and blue eyes (retinal pigment epithelium involved).
• Selenium deficiency in the setting of total parental nutrition can lead to pseudo-albinism.

Hypopigmentation disorders Piebaldism

• Rare autosomal dominant disease
• Congenital white forelock
• Hyperpigmented macules within the amelanotic macules and normally pigmented skin are characteristic.

Hypopigmentation disorders Waardenburg syndrome

An autosomal dominant disorder characterized by the white forelock, heterochromia irides, and hypomelanotic macules.

Conditions Associated with Increased Pigmentation

Question 21. List the differential diagnosis.
Answer:

Hyperpigmentation Systemic Diseases Causing Hyperpigmentation

Skin Tumors

Question 22. Write a short essay/answer on benign, premalignant conditions of the skin.
Answer:

Benign and Premalignant Lesions of Skin

Malignant Skin Tumors

Question 23. Write a short essay/answer on common malignant skin tumors.
Answer:

Malignant tumor of the skin is the most common malignancy in fair-skinned populations.

Categories

Malignant Skin Tumors Etiology and Pathogenesis of Skin Malignancy

• Sun exposure: UVR (ultraviolet radiation) is the main environmental risk factor for skin cancer.
• Genetic predispositions:
  • Xeroderma pigmentosum
  • Basal cell nevus (Gorlin’s) syndrome
• Cutaneous immune surveillance: Immunosuppressed organ transplant recipients have an increased risk of skin cancer, particularly SCC (squamous cell carcinoma). Patients who have received high numbers of PUVA treatments (>150), which are immunosuppressive, are also at increased risk of skin cancer, particularly SCC.
• Chronic inflammation: It is also a risk factor for SCC, which may arise in chronic skin ulcers/scars.
  Basal Cell Carcinoma (Rodent Ulcer) Basal cell carcinomas (BCC) are the most common slow-growing invasive malignant skin tumor that rarely metastasizes.

Types of Basal Cell Carcinoma

Malignant Skin Tumors types of basal cell carcinoma (BCC).

• Superficial BCC
• Nodular BCC, rodent type (most common type—75%)
• Pigmented BCC
• Sclerosing or morphea from BCC
• Metaphysical
• Recurrent BCC
• Cystic BCC

Malignant Skin Tumors Clinical Presentation

• Incidence of BCCs increases with age on exposed sites and males are more commonly affected.
• Sites: Occur at sun-exposed sites and in fair-skinned people. The usual site is above a line drawn from the angle of the mouth to the pinna of the ear.
• Appear as slow-growing pearly papules or nodules (or rarely be cystic), often containing prominent, dilated subepidermal blood vessels (telangiectasia).
• Advanced tumors may ulcerate to form a crater with a rolled, pearly edge. They locally invade and erode the underlying bone or facial sinuses like a rodent and are known as rodent ulcers. Crusting and bleeding in the center of the tumor are frequently seen.
• They are 10–20 times more common in chronically immunosuppressed solid organ transplant recipients.

Malignant Skin Tumors Squamous Cell Carcinoma

• The second most common skin cancer arising on sun-exposed sites
• More aggressive than basal cell carcinoma, as it can metastasize if left untreated.
• Sex: More common in elderly men than in women
• Clinical presentation: Appear as sharply defined, red, scaling plaques

Malignant Skin Tumors Classification of Malignant Melanoma of Skin 

Clinical signs that help to distinguish malignant from benign moles are presented in.

Malignant Skin Tumors Management/Treatment

Basal cell carcinoma rarely metastasizes. Hence, a metastatic work-up is usually not required.

Malignant Skin Tumors Surgical therapy:

• Surgical excision with controlled borders is often the treatment of choice and recurrence rates are lowest.
• Mohs’ micrographic surgery

Malignant Skin Tumors Nonsurgical therapies:

• Topical photodynamic therapy and topical 5% imiquimod
• cream and 5-fluorouracil
• Cryotherapy: It is a destructive treatment that uses liquid nitrogen
• Radiotherapy
• Hedgehog pathway inhibitors (vismodegib) for advanced
• inoperable BCC
• Curettage and cautery: Occasionally can be used in older patients

Malignant Skin Tumors Risk Factors

• Risk factors for squamous cell carcinoma of the skin.
• Precursors of SCC: Solar/actinic keratoses or Bowen’s disease
• Industrial carcinogens: Tars and oils
• Chronic nonhealing skin ulcers, for Example: chronic osteomyelitis
• Old burn scars (Example: Marjolin’s ulcers)
• Ingestion of arsenicals
• Ionizing radiation or previous X-ray therapy
• Tobacco and betel nut chewing in the oral cavity
• Chronic venous ulcers and discoid lupus erythematosus

Malignant Skin Tumors Clinical Features

Malignant Skin Tumors Sites: Usually occurs on chronically sun-exposed portions of the skin, such as the bald scalp, tops of ears, face, lower lip, and back of hands.

Malignant Skin Tumors Appearance: Depends on histological grading. Well differentiated tumors present as keratotic nodules, whereas
poorly differentiated tumors tend to be ill-defined and infiltrative, often-warty nodules or plaque that may ulcerate.

Malignant Skin Tumors Behavior: They can grow very rapidly. SCC has metastatic potential.

Malignant Skin Tumors Management

• Early diagnosis is important. Regional lymph nodes should be routinely examined particularly for high-risk tumors arising on lips, ears, perinatal regions, or tumors developing at sites of chronic ulceration, burn scars, or sites of previous radiotherapy.
• Complete surgical excision is the usual treatment of choice. Excision with a 3–4-mm margin has a cure rate of about 90–95% for most SCC.
• Other options:
• Curettage and cautery: Curettage should be avoided and is reserved for small, low-risk lesions
• Radiotherapy: If surgery is not feasible
• Medical management is not usually considered for invasive SCC. These include photodynamic therapy, systemic retinoids, imiquimod, and other immunomodulators, new formulations of 5-fluorouracil, diclofenac in hyaluronic acid gel, and ingenol mebutate.

Malignant Skin Tumors Malignant Melanoma

Malignant melanoma is a relatively common and most serious malignant tumor of epidermal melanocytes. Melanoma has
metastatic potential, which can occur early and it causes deaths even in a young individual.

Malignant Skin Tumors Etiology and Pathogenesis

Predisposing factors

1. Sun exposure:

• Melanomas most commonly develop on sun-exposed surfaces, particularly the upper back in men and the back
  and legs in women.
• Lightly-pigmented (pale/fair-skinned) individuals are at greater risk than darkly-pigmented individuals.
  Other environmental factors may also contribute to risk.

2. Inherited genes:

About 10–15% of melanomas are familial and the genetic abnormalities are:
Mutations in tumor suppressor gene: CDKN2A gene, RB gene, PTEN gene, mutations of NRAS and BRAF

3. Other risk factors:

These include multiple melanocytic nevi (>50), sun sensitivity, immunosuppression, giant congenital melanocytic nevi, lentigo maligna, and a family history of malignant melanoma.

Malignant Skin Tumors Clinical Features

Age and gender: It can occur at any age and either sex, but typically affects the leg in females and back in males. It is rare before puberty.

Malignant Skin Tumors Sites

• Skin: It is the most common site and may develop in the trunk, leg, face, sole, palm, and nail beds.
• Other sites: Oral and anogenital mucosal surfaces, esophagus, leptomeninges, eye, and the substantia nigra

Classification of Malignant Melanoma of Skin

Malignant Skin Tumors Classification of malignant melanoma of the skin.

Malignant Skin Tumors Melanoma without metastatic potential (noninvasive):

• Melanoma in situ
• Lentigo maligna

Malignant Skin Tumors Melanoma with invasive potential:

• Superficial spreading melanoma
• Nodular melanoma
• Acral lentiginous melanoma
• Lentigo maligna melanoma
• Subungual melanoma

Malignant Skin Tumors Management/Treatment

• Surgical excision: For local disease, surgical excision is the only curative treatment.
• Metastatic disease: If there is sentinel node metastasis, surgical resection of lymph nodes, isolated limb perfusion, radiotherapy, immunotherapy (peginterferon α-2b, ipilimumab (anti-CTLA-4), vemurafenib, dabrafenib (BRAF inhibitor), trametinib (MEK inhibitor), pembrolizumab (PD-1 blocker), and chemotherapy may be required.

Malignant Skin Tumors Mycosis Fungoides

Mycosis fungoid (MF) is a cutaneous lymphoma of mature CD4+ T-cells. This is the most common cutaneous T-cell lymphoma. Not all cutaneous T-cell lymphomas are MF.

• Incidence 3 per million (0.29 per 100,000 population in the USA) and 2% of all new cases of NHL
• Age Older adults (55–60 years)
• Male: Female 2:1

Malignant Skin Tumors Clinical Features

• Mycosis fungoides patches are usually distributed in sun-shielded areas such as those covered by a bathing suit or intertriginous regions. The cardinal features of MF are infiltration of the epidermis and then the dermis by atypical cerebriform lymphoid cells Pautrier’s microabscess.
• It is a chronic, slowly progressive disease that evolves from the patch stage to the plaque stage and subsequently to the nodule tumor stage.
• A diagnosis of Sézary syndrome is made when there is a high number of these cells circulating in the peripheral blood in the presence of lymphadenopathy and cutaneous erythroderma occupying >80% of the body surface area.
• Chemotherapy, retinoids, electron beam therapy, and photochemotherapy are used in the treatment.

Phakomatoses

Neurocutaneous Syndromes

Question 24. Write a short note on neurocutaneous syndromes.
Answer:

• They are a group of inherited syndromes characterized by the involvement of the brain and skin (sometimes retina).
• Phakomatoses (or neuro-neurocutaneous syndromes) are multisystem disorders that have a characteristic central nervous system, ocular and cutaneous lesions (embryologically all originate from ectoderm) of variable severity.

Neurocutaneous Syndromes Common Neurocutaneous Syndromes

• Neurofibromatosis 1 and 2
• Tuberous sclerosis
• Von Hippel–Lindau disease
• Sturge–Weber syndrome
• Klippel–Trenaunay–Weber syndrome
• Osler–Weber–Rendu syndrome
• Wyburn–Mason syndrome
• Linear sebaceous nevus syndrome
• Neurocutaneous melanosis
• Waardenburg syndrome type 1 and 2
• Fabry’s disease
• Lentiginosis, deafness, and cardiopathy syndrome
• Hypomelanosis of Ito
• Ataxia–telangiectasia (Louis–Bar syndrome)
• Xeroderma pigmentosum
• Cockayne’s syndrome
• Rothmund–Thomson syndrome
• Sjögren–Larsson syndrome
• Neuroichthyosis
• Werner syndrome and Progeria
• Incontinentia pigmenti
• Neurocutaneous melanosis
• Retinal-neurocutaneous cavernous hemangioma syndrome (Weskamp–Cotlier syndrome)

Neurofiromatosis Type 1

Question 25. Write a short note on neurofibromatosis.
Answer:

• Synonyms: von Recklinghausen disease and Watson disease
• An autosomal-dominant neurogenetic disorder
• NF1 affects about 1 in 3000 people. Neurofibromatosis type I (NF1) is caused by a mutation in the neurofibromin gene located on chromosome 17, at the band q11.2.

Neurofiromatosis  Diagnostic Criteria for Neurofibromatosis Type 1 

Three subtypes of neurofibromas exist: Cutaneous, subcutaneous, and plexiform. Freckles can be present since birth or sometimes appear later in life especially in the intertriginous region (Crowe’s sign).

Buttonhole sign: Molluscum fibrosum—small, superficial, soft, skin-colored to darker, dome-shaped nodules, which can be pushed through a defect in the skin.

Neurofiromatosis Type 2

• Neurofibromatosis type 2 (NF2) is associated with abnormalities of the NF2 gene, which is located on chromosome 22.
• The NF2 gene produces merlin, also known as schwannoma, a cell membrane-related protein that acts as a tumor suppressor. NF2 has an estimated birth frequency of 1 in 33,000 to 40,000.

Neurofiromatosis Diagnostic criteria for neurofibromatosis type 1.

• Two or more of the following clinical features must be present:
• Six or more café-au-lait macules of >5 mm in greatest diameter in prepubertal individuals, and >15 mm in greatest diameter in postpubertal individuals
• Two or more neurofibromas of any type or one plexiform neurofibroma
• Freckling in the axillary or inguinal regions
• Optic glioma
• Two or more iris hamartomas (Lisch nodules)
• The distinctive bony lesion, such as sphenoid dysplasia, or thinning of the long bone cortex with or without pseudoarthrosis
• A first-degree relative (parent, sibling, or offspring) with NF1 based on the above criteria

Neurofibromatosis Diagnostic criteria for NF2 are listed.

Neurofiromatosis  Diagnostic criteria for neurofibromatosis type 2.

• Bilateral vestibular schwannomas
• A first-degree relative with NF2 and:
  • Unilateral vestibular schwannoma or
  • Any two of meningioma, schwannoma, glioma, neurofibroma, and posterior subcapsular lenticular opacities
• Unilateral vestibular schwannoma and
  • Any two of meningioma, schwannoma, glioma, neurofibroma, and posterior subcapsular lenticular opacities
• Multiple meningiomas and
  • Unilateral vestibular schwannoma or
  • Any two of—schwannoma, glioma, neurofibroma, and cataract
• Any two of = Two individual tumors or cataract.

Tuberous Sclerosis

Question 26. Write a short note on tuberous sclerosis.
Answer:

• Tuberous sclerosis complex is an inherited neurocutaneous disorder characterized by pleomorphic features involving many organ systems, including multiple benign hamartomas of the brain, eyes, heart, lung, liver, kidney, and skin.
• It is called Bourneville disease, as it was first described by him in 1880.
• The clinical triad of Vogt—EPI-LOI-A: Epilepsy, low intelligence, and adenoma sebaceous.
• Incidence 1 in 6,000–9,000
• Dominant inheritance but a high frequency of spontaneous mutation

Diagnostic criteria for tuberous sclerosis complex are given.

Café-au-lait Macules

Question 27. Write short note on café-au-lait macules (CALMs).
Answer:

• These are well-circumscribed, evenly pigmented macules; size ranges from 1 to 2 mm to >20 cm.
• Microscopically shows increased melanin in both melanocytes and basal keratinocytes.
• In McCune–Albright syndrome, CALM may have a block-like distribution with midline demarcation and an irregular, jagged outline (“coast of Maine”).
• In NF1, there are more numbers of CALM, and has a more widespread distribution (with the exception of segmental NF1), which is “typical” based on their regular borders, smooth (“coast of California”), and uniform pigmentation. In adults, the presence of six or more café-au-lait macules is highly suggestive of NF1.
• In fair-skinned infants, they may be difficult to detect on routine physical examination but are accentuated with examination under a Wood’s lamp.
• CALMs may be observed in tuberous sclerosis, ataxia telangiectasia, Bloom’s syndrome, and Watson’s syndrome.

Disorders Of Skin Appendages

Acne Vulgaris

Question 28. Write a short note on the etiology, clinical features, and management of acne vulgaris.
Answer:

• Acne is a multifactorial disease characterized by abnormalities in sebum production, follicular desquamation, bacterial proliferation, and inflammation.
• Age and gender: It starts after puberty and is seen primarily in teenagers (1220 years of age) and young adults. 85% adolescents experience it. The prevalence of comedones in adolescents approaches 100%. But, it can persist into the thirties and forties, particularly in females.
• It affects both males and females, although males tend to have more severe disease. Cutibacterium acnes, Staphylococcus epidermis, and Malassezia furfur induce inflammation and induce follicular epidermal proliferation.

Acne Vulgaris Clinical Features

• Sites: Most common location for acne is the face, but it may involve the chest and back (trunk).
• Greasiness of the skin (seborrhea) is often observed.
• Type of lesions: The hallmark is the comedone.

Acne Vulgaris Microcomedone

• Hyperkeratotic plug made of sebum and keratin in the follicular canal
• These comedones may be noninflammatory or inflammatory type (open or closed comedones)
• Open comedones (blackheads) appear as black papules due to the keratin debris and closed comedones (whiteheads) usually have no visible follicular opening. Inflammatory papules, nodules, and cysts may arise from comedones.

Acne Vulgaris Sequelae: Most cases remain mild and do not lead to scarring.

Few may develop large inflammatory cysts and nodules and may heal by significant scarring. Solid facial edema (Morbihan’s disease) is a rare complication of acne that presents as facial soft-tissue edema and erythema. Postinflammatory hyperpigmentation and bacterial folliculitis can be seen.

Acne Vulgaris Grading of acne

• Grade 1: Comedones. They are of two types—open and closed. Open comedones are due to the plugging of the pilosebaceous orifice by sebum on the skin surface. Closed comedones are due to keratin and sebum plugging the pilosebaceous orifice below the skin surface
• Grade 2: Inflammatory lesions present as a small papule with erythema.
• Grade 3: Pustules
• Grade 4: Many pustules coalesce to form nodules and cysts

Acne Vulgaris Management

Acne Vulgaris Mild-to-moderate disease

Acne Vulgaris Local therapy:

• Areas affected with acne should be kept clean by regular washing with soap and water. However, vigorous scrubbing may cause mechanical rupture of comedones.
• Topical agents such as benzoyl peroxide (most cost-effective therapy), retinoids [tretinoin (most potent keratolytic agent), adapalene (less irritating), or tazarotene], or salicylic acid should be used.
• Topical antibacterial agents: Inflammatory acne responds to topical antibacterial agents such as azelaic acid, topical erythromycin, or clindamycin.
• Topical Dapsone

Systemic therapy:

• Antibiotics: Moderate inflammatory acne will benefit from the addition of systemic therapy such as oral tetracycline (oxytetracycline or lymecycline), doxycycline (200 mg/day), or minocycline (200 mg/day) for 3–6 months.
• Hormonal therapy: These include estrogen-containing oral contraceptives or a combined estrogen/anti-androgen (such as cyproterone acetate) contraceptive.

Moderate-to-severe disease

• Isotretinoin: Moderate-to-severe acne or if there is no adequate response to 6 months of therapy with the other therapies (combined systemic and topical approaches), patients should be considered for isotretinoin (13-cis-retinoic acid).
• Mechanism of action: It decreases sebaceous gland size and sebum excretion, decreases follicular hyper cornification, and reduces P. acnes colonization.
• Side effects: Oral isotretinoin is teratogenic (prevent pregnancy while taking isotretinoin), and possibly associated with risk for severe depression, pseudotumor cerebri, and other significant side effects.

Other treatments and physical measures:

Acne Vulgaris For inflamed acne nodules or cysts: They may require intralesional injections of triamcinolone acetonide or incision and drainage, or excision under local anesthesia.

Scarring: Prevention of scarring by adequate treatment of active acne. Keloid scars respond to intralesional steroid injection and/or silicone dressings. Other measures for scarring include carbon dioxide laser, microdermabrasion, chemical peeling, or localized excision.

 Acne Vulgaris UVB phototherapy: They are rarely used in patients with inflammatory acne who are unable to use conventional therapy, such as isotretinoin.

Acne Vulgaris Clinical variants

• Acne conglobata is rare and commonly affects adult males. It is a severe form of acne characterized by numerous comedones, large abscesses with sinuses, and grouped inflammatory nodules associated with suppuration.
• It may be associated with hidradenitis suppurativa (a chronic, inflammatory disorder of apocrine glands, mainly affecting axillae and groins), folliculitis, and pilonidal sinus.
• Acne fulminans is a rare, severe variant of acne, usually affecting the trunk in adolescent males. It presents with fever, arthralgias, and systemic inflammation, with leukocytosis and raised plasma viscosity.
• Acne excoriée (also known as “picker’s-acne”) is self-inflicted excoriations produced by compulsive picking of preexisting or imagined acne lesions. It is usually observed in teenage girls with psychological problems.
• SAPHO syndrome: Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis syndrome
• Acne venenata: Contact with acnegenic chemicals can produce comedones. For example, chlorinated hydrocarbons, cutting oils, petroleum oil, and coal tar
• Acne aestivalis (Mallorca acne): It is rare and seen in females 25–40 years. It starts in spring and resolves by fall characterized by small papules on cheeks, neck, and upper body. Comedones and pustules are sparse or absent.

Hair Disorders

Question 29. List the causes of alopecia.
Answer;

Hair Disorders Alopecia: Alopecia is defined as the “absence or loss of hair”. It is a chronic disorder secondary to the disease of either the hair follicle, hair shaft, or scalp.

Hair Disorders Alopecia

Hair Disorders Classification and Causes of Alopecia

Hair Disorders Alopecia Areata

Definition: Rapid and complete loss of hair in one or most often several round or oval patches, usually on the scalp, bearded area, eyebrows, eyelashes, and less commonly on other hairy areas of the body.

Approximately 1.7% of the population will experience an episode of alopecia areata during their lifetime.

Hair Disorders Etiology

It is an autoimmune disease:

• Mediated by the cellular arm (T-cell and macrophages)
• Modified by genetic factors (HLA-R4, DR11, and DQ7)

Hair Disorders Stages of Alopecia Areata

• Acute hair loss
• Persistent (chronic) baldness
• Partial telogen to anagen conversion (incomplete recovery)
• Normal recovery

Hair Disorders Clinical features

• Rapid and complete loss of hair in one or several patches
• Site: Scalp, bearded area, eyebrows, eyelashes, and less commonly other areas of the body
• Size: Patches 1–5 cm in diameter
• Exclamation point hairs, short broken hairs for which the proximal end of the hair is narrower than the distal end, are pathognomonic findings in alopecia areata.

Hair Disorders Alopecia totalis is a more advanced form of alopecia areata, which results in total loss of all hair on the scalp.

Hair Disorders Alopecia universalis is the most advanced form of alopecia areata, which results in total loss of all hair on the body, including eyelashes and eyebrows.

Hair Disorders Alopecia barbae is alopecia areata that is localized to the beard area. It can be a single bald patch or more extensive hair loss across the whole of beard area.

Hair Disorders Androgenetic Alopecia

• It is a thinning of the hair to an almost transparent state in both men and women.
• It is hereditary.
• In both men and women, it is linked to having an excess of male hormones (androgens) around the hair follicles, which can block hair growth.
• Women are more likely to develop androgenic alopecia after menopause when they have fewer female hormones.

Hair Disorders Investigations

• Blood investigations: Complete blood count, serum ferritin, blood sugar, renal and liver function, hormones (thyroid, FSH, LH, and testosterone), vitamin B12, and vitamin D
• Trichometric analysis: The follis cope can magnify these images by up to 100 times, giving doctors a detailed look at hair, hair follicles, and the scalp
• Fungal culture
• Punch biopsy is used to distinguish between the types of cicatricial, or scarring, alopecia.
• Daily hair counts:
  • Useful for quantitative assessment of the actual number of hairs shed daily in patients with complaints of excessive shedding. Collect for 14 consecutive days
  • Average daily loss of 30 70 hairs/day
  • If >70 hairs a microscopic examination is done to detect pathology

Hair Disorders Treatment

• Many cases of hair loss are temporary, for example, due to chemotherapy, or they are a natural part of aging and do not need treatment.
• If hair loss is caused by an infection or another condition, treating the underlying problem may help to prevent further hair loss
• Spontaneous recovery is extremely common for patchy alopecia areata.
• Steroid: Both local (intralesional and topical) and systemic (in short course)
• Topical 1% anthralin cream: Applied for 15–20 minutes and then shampooed off the treated side
• 5% topical minoxidil: As a single agent or as an adjuvant with topical anthralin
• Puva
• Contact sensitizer: Squaric acid dibutyl ester, diphencyprone, and dinitrochlorobenzene
• Finasteride: It acts by preventing the hormone testosterone from being converted to the hormone dihydrotestosterone (DHT). DHT causes the hair follicles to shrink, so blocking its production allows the hair follicles to regain their normal size.
• Psychological support
• Hair transplantation is a surgical technique that removes hair follicles from one part of the body, called the “donor site”, to a bald or balding part of the body known as the “recipient site”. The technique is primarily used to treat male pattern baldness.
• Follicular unit transplantation (FUT) is a hair restoration technique, also known as the strip procedure, where a patient’s hair is transplanted in naturally occurring groups of 1–4 hairs, called follicular units.

Leg Ulcers

Question 30. Write a short note on the causes of nonhealing leg ulcers.
Answer:

Ulceration of the skin is defined as complete epidermal loss. It results in exposure of dermal (or deeper) layers.

Causes of Leg Ulcers

Xerostomia

Question 31. Write a short note on xerostomia.
Answer:

• Normal healthy adults daily produce about 1,500 mL of saliva.
• Xerostomia is characterized by dry mouth and may be due to a decrease in the production of saliva.

Xerostomia Effects of Xerostomia

• Symptoms may be minor or may hamper activities of daily living.
• May produce a burning sensation in the mouth, difficulty in eating, chewing, and swallowing
• May produce tooth decay, bad breath, candida infection, and viral infections (E herpes simplex)

Xerostomia Etiology

• Anticholinergic drugs (reduce the volume of saliva): For example, anticholinergics, antidepressants, antipsychotics, antiemetics, antihistamines, antihypertensives, antiparkinsonian drugs, antispasmodics, and diuretics.
• Sympathomimetic drugs (produce viscous saliva): For example, amphetamines, appetite suppressants, decongestants, and bronchodilators
• Systemic diseases: Addison’s disease, Alzheimer’s disease, salivary gland infection, Sjögren’s syndrome, alcoholic cirrhosis, diabetes mellitus, HIV/AIDS, radiation to head and neck region (Example: for cancer therapy), and severe dehydration.
• Other causes: Elderly individuals, sleep-related xerostomia (due to mouth breathing during sleep).

Xerostomia Management

• Stop the offending drug
• Frequent sips of water and teeth brushing
• Oral hygiene: Chlorhexidine rinses
• Artificial salivary substitutes: They act as lubricants and protective and not as substitutes for digestive and enzymatic actions (Example: sodium carboxymethyl cellulose, potassium dihydrogen orthophosphate, and sorbitol).
• Cholinergic agonists:
• Pilocarpine and cevimeline: It should be cautiously used in patients with cardiovascular disease and chronic respiratory conditions. They are contraindicated in patients with uncontrolled asthma, angle-closure (narrow-angle) glaucoma, and liver disease.

Pruritus

Question 32. Write a short essay/note on pruritus/generalized pruritus and its causes.
Answer:

The terms “itch” and “pruritus” are used synonymously; however, “pruritus” is often used for generalized itch.

Pruritus Definition: Itch is an unpleasant cutaneous sensation that leads to scratching or rubbing.

Pruritus Causes

Pruritus Dermatological causes of pruritus.

• Atopic dermatitis
• Scabies
• Xerosis
• Lichen simplex chronicus
• Contact dermatitis
• Insect bites
• Sunburn
• Ichthyoses
• Dermatitis herpetiformis
• Psoriasis
• Lichen planus
• Fungal infections
• Pediculosis
• Plaster of Paris casts

Pruritus Management/Treatment

• General measures:
• Avoid soap
• Control of xerosis with moisturizers and humidification of the indoor environment
• Specific measures:
• Establish the diagnosis and treat the underlying skin or systemic disease
• If a clear-cut diagnosis is not possible, various nonspecific measures can be used for symptom control. It is necessary to reassess intermittently in order to avoid missing the diagnosis.
• UVB (ultraviolet B) phototherapy in chronic kidney disease
• Ursodeoxycholic acid (UDCA) in cholestasis
• Cholestyramine, rifampicin, and opioid antagonists (Example: naltrexone) in primary biliary cirrhosis
• Corticosteroids in Hodgkin’s disease
• Paroxetine (selective serotonin reuptake inhibitor) in itching as a paraneoplastic manifestation of malignancies
• Symptomatic measures:
• These include sedation, often with H1 antagonist antihistamines, emollients, and counter-irritants (such as topical menthol-containing preparations).
• Intractable cases: Phototherapy, low-dose tricyclic antidepressants (e.g., amitriptyline), or gabapentin may help.
• Complications of pruritus:
• Prurigo nodularis is a variant of lichen simplex chronicus in which nodules develop at the site of scratching.
• Local infection due to scratching
• Lichen simplex chronicus is localized skin thickening produced due to intense scratching

Pruritus Panniculitis

• Panniculitis is an inflammatory reaction in the subcutaneous fat tissue.
• Panniculitis may preferentially affect

1. the lobules of fat (lobular panniculitis with necrosis and purpura) or
2. the connective tissue that separates fat into
3. lobules (septal panniculitis).

Erythema Nodosum

Question 33. Write a short essay/note on the etiology, clinical features, diagnosis, and treatment of erythema nodosum.
Answer:

• Erythema nodosum (septal panniculitis) is the most common form of panniculitis.
• It is also called subacute migratory panniculitis of Vilanova and Piñol.

Erythema Nodosum Etiology

Factors provoking erythema nodosum: The occurrence of erythema nodosum is often associated with provoking factors. Most often, it is idiopathic without any identifiable underlying cause.

Erythema Nodosum Clinical Features

Age and gender: Age 20–30 years but any age group may be affected. The female-to-male ratio is 3–6:1.

Lesions

Erythema Nodosum Diagnosis

• Most often based on clinical presentation
• Deep wedge biopsy including the subcutis is usually required for histologic diagnosis. Histologically shows inflammation of the connective tissue septa in the subcutaneous fat tissue (septal panniculitis). Vasculitis is not observed.
• Identification of triggering factors causing erythema nodosum:
• Complete blood count (CBC) with differential ESR (erythrocyte sedimentation rate) and C-reactive protein level
• Evaluation for β-hemolytic streptococcal infection: Throat culture for group A streptococci, rapid antigen test, antistreptolysin-O titer, and polymerase chain reaction assay
• Chest radiograph, Example: to detect tuberculosis and sarcoidosis—Mantoux test
• Stool examination for ova and parasites, for Example: in patients with GIT symptoms
• Evaluation for inflammatory bowel disease in patients with symptoms of IBD

Erythema Nodosum Treatment

• Identify and remove/treat any underlying cause (treatment of tuberculosis/IBD/sarcoid).
• Bed rest, leg elevation, and analgesics with NSAIDs may produce symptomatic relief. However, avoid NSAIDs, if secondary to Crohn’s disease because they may trigger a flare-up of the underlying Crohn’s disease.
• Systemic corticosteroids must be avoided in cases of infection and malignancy.
• Dapsone and potassium iodide orally (400–900 mg/day) have been effective for stubborn disease (if NSAIDs do not relieve pain or the lesions persist) for symptomatic relief. Recalcitrant, chronic, or recurring EN is treated with thalidomide, colchicine, and hydroxychloroquine.

Leprosy

Question 34. Classify and describe the epidemiology, etiology, microbiology pathogenesis, clinical presentations, and diagnostic features of leprosy.
Answer:

Definition: Leprosy (Hansen’s disease) is a chronic, granulomatous, slowly progressive, destructive infection affecting skin and nerves, caused by Mycobacterium leprae.

Leprosy Epidemiology

• The WHO launched a 5-year “Global Leprosy Strategy 2016–2020” in April, 2016 titled “accelerating towards a leprosy-free world”.
• In India, the National Leprosy Eradication Programme (NLEP) is the centrally sponsored health scheme of the Ministry of Health and Family Welfare, Government of India.
• India continues to account for 60% of new cases reported globally each year and is among the 22 “global priority countries” that contribute 95% of world numbers of leprosy warranting a sustained effort to bring the numbers down.
  • Mode of transmission:
  • Inoculation/inhalation and

1. Intimate contact
2. Incubation period: Generally 2–7 years

Leprosy Bacteriological Considerations

• Mycobacterium leprae is an acid and alcohol-fast, intracellular bacillus.
• Lepra bacilli survive and grow better at a temperature below that of the internal organs (close to 30°C rather than 37°C).
• Hence, it affects sites such as skin, peripheral nerves, the mucosa of the upper airways, and other tissues (bone, eyes, testis, and some viscera).
• Mycobacterium leprae can be grown in the footpads of mice and nine-banded armadillos. Cannot be cultured on
  artificial media or in cell culture.

Leprosy Classification

In the early stage, the disease may be indeterminate and may either spontaneously undergo remission or develop into overt leprosy.

1. Ridley and Jopling’s (1966) classification: It depends on the clinicopathological spectrum of the disease, which is determined by the immune resistance of the host.

• Tuberculoid leprosy (TT): It is the polar form that has a maximal immune response. It is characterized by single or few sharply demarcated skin lesions with predominant peripheral nerve involvement. The bacilli are usually absent or difficult to demonstrate.
• Borderline tuberculoid (BT): In this type, the immune response falls between BB and TT.
• Borderline leprosy (BB): It exactly falls between two polar forms of leprosy.
• Borderline lepromatous (BL) has an immune response that falls between BB and LL.
• Lepromatous leprosy (LL): It is the other polar form with the least immune response. This is characterized by extensive, diffuse, and bilaterally symmetrical skin lesions that contain numerous bacilli. The peripheral nerves are better preserved than in the tuberculoid form.
• Indeterminate type: When the biopsy sample shows definite diagnostic evidence of leprosy (both nerve involvement and acid-fast bacilli) but clinically not fitting to the leprosy spectrum.

2. WHO classification:

• Paucibacillary: All cases of tuberculoid leprosy and some cases of borderline type
• Multibacillary: All cases of lepromatous leprosy and some cases of borderline type bacilli are present in large numbers, hence the term multibacillary (MB).

Clinical Features

Tuberculoid Leprosy

Question 35. Discuss the clinical features of tuberculoid leprosy.
Answer:

• Skin lesions: The early features consist of one or few, localized, well-demarcated, dry, elevated, hypoesthetic, red, or hypopigmented macules. Later, the lesions become larger, margins elevated, and circinate or gyrate. Fully developed lesions are anesthetic and show loss of sweat glands and hair follicles.
• Nerve involvement: occurs early and is the dominating feature in tuberculoid leprosy. It is usually asymmetric and the involved nerves are thickened and palpable.
• Routinely, the nerves such as the ulnar, peroneal (lateral popliteal), and greater auricular nerves should be palpated. Sometimes, TT may present with only nerve involvement without any skin lesions (neural leprosy or pure neuritic leprosy).
• Consequences (complications) of nerve involvement are:
• Sensory nerve involvement produces sensory dysfunctions such as glove and stocking anesthesia (more common in LL), chronic nonhealing, plantar ulcers, and repeated injuries to hands and feet (leading to autoamputation of fingers or toes).
• Motor nerve involvement produces muscle weakness, wasting, and later paralysis followed by contractures. Nerves involved and their consequences are as follows:
  • Ulnar nerve: Claw hand (main en griffe)
  • Median nerve: Ape hand (main de singe)
  • Lateral popliteal nerve: Foot drop
  • Posterior tibial nerve: Claw toes or hammer toes
• Autonomic involvement produces anhidrosis or hyperhidrosis
• Cranial nerve involvement: Facial nerve is commonly affected and results in facial paralysis, lagophthalmos, exposure keratitis, and corneal ulcerations (may lead to blindness).
• Trigeminal nerve involvement may develop early causing loss of corneal reflex. Greater auricular nerve , supraorbital, supratrochlear, and infraorbital nerves are also thickened.

Lepromatous Leprosy

Question 36. Discuss the clinical features of multibacillary/lepromatous leprosy.
Answer:

• Nasal symptoms are the early features of LL and include anosmia, nasal stuffiness, crust formation, and blood-stained nasal discharge.
• Skin lesions include multiple, symmetric, macules, papules, plaques, or nodules. The macules are often hypopigmented.
• The borders of the lesions are ill-defined, centers indurated, raised, and convex (“inverted saucer” appearance).
• There is also diffuse infiltration between the lesions. The nodular skin lesions may ulcerate. The lesions are more common on the face (cheeks, nose, and eyebrows) (Fig. 22.31A), ears, wrists, elbows, buttocks, and knees. With progression, the nodular lesions in the face and ear lobes (Fig. 22.31B) may coalesce to produce a thickening of the face and corrugated forehead.
• This produces a lion-like appearance known as leonine facies (Fig. 22.31C). This may be accompanied by loss of eyebrows and eyelashes.
• Nerve involvement of major nerve trunks is less prominent in LL. In advanced disease, loss of sensation with “glove and stocking” anesthesia is common. Mononeuritis multiplex can also occur.
• Lepromatous leprosy without visible skin lesions but with diffuse dermal infiltration and a demonstrable thickening of the dermis is called diffuse lepromatosis.
• Bone involvement: It may develop in the hands, feet (phalanges, metatarsals, and tarsal bones), and skull. It causes slow absorption of distal phalanges resulting in shortening of fingers.
• In the skull, it may produce atrophy of the anterior nasal spine (leading to nasal collapse) and atrophy of the maxillary alveolar process (causing loosening and loss of upper incisors). These changes in the skull produce “facies leprosa”.

Lepromatous Leprosy Other features:

• Bilateral edema of legs and ankles
• Saddle nose: Swollen and broad nose, septal perforation, and nasal collapses produce saddle nose deformity.
• Teeth: Loosening of upper incisor teeth, which may later fall off
• The anterior chamber of the eye involvement results in keratitis, iridocyclitis, and blindness.
• Upper airways: Chronic nasal discharge, laryngitis, palatal perforation, and hoarseness (voice change).
• Testes: Usually severely involved, leading to the destruction of the seminiferous tubules, testicular atrophy, impotence, infertility, and gynecomastia.
• Painless lymphadenopathy involving inguinal and axillary lymph nodes
• Renal lesions: Secondary glomerulonephritis, interstitial nephritis, pyelonephritis, and renal amyloidosis

Question 37. Enumerate and describe the complications of leprosy and its management.
Answer:

Complications of lepromatous leprosy are summarized.

Leprosy and its management Borderline Leprosy

Clinical features are poorly defined and these overlap with features of other subtypes.

Leprosy and its management Reactions in Leprosy or Lepra Reactions

Immunity in leprosy may change spontaneously or following treatment. The course of leprosy may be interrupted by lepra reactions, which comprise several common immunologically mediated inflammatory states.

There are two types of lepra reactions. Both types of reactions can occur in untreated patients, but more often develop as complications of chemotherapy.

Type I Lepra Reaction

Question 38. Enumerate, describe, and identify lepra reactions and supportive measures and therapy of lepra reactions.
Answer:

Type I Lepra Reaction Borderline leprosy (BT, BB, or BL) is the most unstable form of leprosy where immune status may shift up or down, and type I reaction occurs in 50% of these patients. These are delayed hypersensitivity reactions and may be of two types:

Type I Lepra Reaction Downgrading reaction and reversal reaction.

1. Downgrading reaction: If type 1 lepra reactions precede the initiation of appropriate antimicrobial therapy, they are termed downgrading reactions. It is associated with a decrease in immunity and histologically the disease moves (usually from borderline) toward lepromatous leprosy.
2. Upgrading/reversal reaction: If type I lepra reactions occur after the initiation of antimicrobial therapy, they are termed reversal reactions. It is associated with improved immunity and histologically the disease moves (usually from borderline) toward tuberculoid leprosy.

It develops usually in the 1st month or year after the initiation of therapy but may also occur after several years.

Type I Lepra Reaction Manifestations: Existing skin lesions (i.e., macules, papules, and plaques) develop classic signs of inflammation in the form of erythema and swelling and new skin lesions may appear.

Peripheral nerve inflammation (i.e., neuritis) causes pain and exquisite tenderness of nerves. Irreversible nerve damage may occur suddenly (24 hours) unless the reaction is treated promptly.

Type I Lepra Reaction Type 2 Lepra Reaction or Erythema Nodosum Leprosum

It occurs mostly in lepromatous leprosy (BL/LL), particularly within 2 years of the institution of chemotherapy. It develops due to widespread immune-complex deposition (type III hypersensitivity reactions) and overproduction of tumor necrosis factor (TNF-α).

Manifestations

• Crops of painful, tender inflamed, red, subcutaneous papules or plaque (on the face and limbs) that resolve spontaneously in a few days to a week but new crops may appear.
• Severe reactions may be accompanied by low-grade fever, malaise, lymphadenopathy symptoms of neuritis, and arthralgia.
• Other features include uveitis, iritis, orchitis, myositis, glomerulonephritis, edema, anemia, leukocytosis, and abnormal liver function tests.

Type I Lepra Reaction Diagnosis of Leprosy

• Clinical diagnosis is by cardinal signs of leprosy: Hypopigmented/reddish patches with loss of sensation and thickening of peripheral nerves
• Slit-skin smears: The smears are made from skin lesions (earlobes and dorsum of the ring or middle finger) by scrapedincision method and the dermal material (fluid obtained) onto a glass slide and stained for acid-fast bacilli (AFB). It is useful in borderline lepromatous (BL) and LL.
• Nasal secretions for AFB from LL show numerous bacilli.
• Lepromin test: Lepromin is an antigen extract of dead M. leprae. The test is performed like the tuberculin test by intradermal injection of lepromin but is read after 4 weeks.
• It is not a diagnostic test for leprosy. It is used for classifying leprosy based on the immune response. It is interpreted as follows:
  • Lepromatous leprosy shows a negative lepromin test due to suppression of cell-mediated immunity.
  • Tuberculoid leprosy shows a positive lepromin test because of delayed hypersensitivity reaction.
  • Borderline leprosy: Negative or weakly positive responses
• Skin biopsy: Involvement of peripheral nerves in a skin biopsy taken from the affected area is pathognomonic, even in the absence of bacilli. Lepra bacilli can be demonstrated in LL and BL types by Fite–Ferraro stain.
• The serological test is not sensitive or specific enough for diagnosis.
  • Hypergammaglobulinemia is common in LL and can give false-positive serological tests (VDRL, rheumatoid factor, and antinuclear antibodies).
  • IgM antibodies to PGL-1 (phenolic glycolipid-1) may be found in 95% of LL and in 60% of TT. However, these antibodies may also be present in normal individuals.
• PCR testing for M. leprae DNA: Detection of M. leprae DNA is possible in all types of leprosy using the polymerase chain reaction, but not sensitive or specific enough for diagnosis. It can be used to assess the efficacy of treatment.

Question 39. Enumerate the indications and describe the pharmacology, administration, and adverse reaction of pharmacotherapies for various classes of leprosy based on national guidelines.
(or)Describe the treatment of leprosy based on the World Health Organization (WHO) guidelines.
Answer:

Multibacillary leprosy (MB): Duration of treatment is 1 year/12 months

• Regimen 1:
  • Dapsone 2 mg/kg daily (maximum 100 mg)
  • Clofazimine 50 mg daily or 100 mg three times a week
  • Rifampicin, 450 mg (for patients <35 kg) or 600 mg (for patients <35 kg), on 2 consecutive days in a month
• Regimen 2:
  • Dapsone 100 mg daily (self-administered)
  • Clofazimine 50 mg daily (self-administered) + 300 mg once a month (supervised)
  • Rifampicin 600 mg once a month (supervised)

Paucibacillary leprosy (PB): Duration of treatment is 6 months

• Dapsone 100 mg given daily
• Rifampicin 600 mg is given once a month under supervision.
• Clofazimine 50 mg daily (self-administered) + 300 mg once a month (supervised) New addition in 2020

Multibacillary leprosy (MB) Treatment

Multibacillary leprosy (MB) Drugs

• The main drugs available include dapsone (100 mg), rifampicin (600 mg), clofazimine (100 mg), ethionamide (500 mg), and thiacetazone (150 mg). Other drugs effective against leprosy are ofloxacin, minocycline, and clarithromycin.
• The side effects of various drugs are as follows:
  • Dapsone: Hemolysis, agranulocytosis, hepatitis, and exfoliative dermatitis
  • Clofazimine: They are mainly found in the skin (For example reddish pigmentation of skin and ichthyosis) and intestinal tract (For example diarrhea and cramping abdominal pain).

Multibacillary leprosy (MB) Treatment regimens for leprosy

There are two recommended regimens for multibacillary and one for paucibacillary leprosy

Multibacillary leprosy (MB) Treatment of lepra reactions.

During lepra reactions, the chemotherapy for leprosy is maintained.

1. Type 1 lepra reaction (reversal reaction):

• Mild cases: Aspirin 600 mg 6 hourly
• Severe cases: Start with prednisone 40–80 mg daily and reduce gradually over 3–9 months

2. Type 2 lepra reaction (erythema nodosum leprosum):

• Mild cases: Aspirin 600 mg 6 hourly
• Severe cases: Prednisone 1 mg/kg/day. If there is no response to steroids, add clofazimine (300 mg/ day) or thalidomide (100 mg 4 times daily). The doses are slowly reduced over 1–3 months. If there is involvement of eyes, 1% hydrocortisone drops or ointment and 1% atropine drops is given.

Multibacillary leprosy (MB) Ectoparasites

Ectoparasites are parasites that live on the surface of its host.

Scabies

Question 40. Discuss the clinical features and management of scabies.
Answer:

Scabies is an intensely itchy rash caused by the ectoparasitic mite, Sarcoptes scabiei var. hominis.

Scabies Age: It is most common in children and young adults but can occur in any age group.

Scabies Mode of Transmission

• Person-to-person contact: Scabies is highly contagious. Newly fertilized female mites are transmitted from person to person by prolonged close/intimate personal contact (Example: within households or institutions) with the skin and by sexual contact.
• This transmission is facilitated by social crowding, poor hygiene, and multiple sexual partners. In the absence of host contact, the mites usually die within a day or so. About 15–20 minutes of close contact with an infected individual is necessary for the transfer of the mites from one individual to another.
• Through contaminated clothes: Transfer through clothes and bedding contaminated by the infested patient immediately
  beforehand.

Scabies Clinical Features

• Scabies clinically presents with itchy red papules (or occasionally vesicles and pustules). Itching/pruritus is worse at night.
• Distribution of lesions: It often suggests the diagnosis. Skin lesions can occur anywhere but rarely on the face and scalp, except in infants. Sites of predilection are
• Between the web spaces of the fingers and toes,
• On the palms and soles (more commonly in small children),
• Around the wrists and axillae, on the male genitalia, and around the nipples and umbilicus. The Circle of the Hebra is an imaginary circle intersecting sites of predilection and includes areolae, axillae, elbow flexures, wrists, finger webs, umbilicus, lower abdomen, and genitalia.
• Pruritus/itching is a prominent feature and is usually intense and worse (most severe) at night and after a hot shower. The itching develops a few days after infestation. It may develop within a few hours if the mite is infested for a second time. It develops in the trunk and limbs, and usually not affects the scalp.
• Generalized rash of scabies appears as tiny red intensely itchy bumps on the limbs and trunk. It is due to an allergic reaction to the mites and their products. It may develop several weeks to develop after the initial infestation.
• Nodules: The presence of itchy lumps or nodules in the armpits and groins or along the shaft of the penis is highly suggestive of scabies. Nodules may persist for several weeks or longer even after the successful eradication of living mites.
• Acropustulosis: Blisters and pustules on the palms and soles of infants
  with scabies.

Scabies Pathognomonic sign: It is the presence of linear or curved skin burrows in which the mites live. However, these are not always seen. Burrows are seen as dark wavy lines in the epidermis and measure up to 15 mm. Typical burrows may be only a few in number.

Hence, they are often missed, if the skin has been scratched or become secondarily infected or if there is eczema. Microscopic examination of the contents of a burrow may show many mites, eggs, or mite feces (scybala).

Scabies Complication: Excoriations and secondary bacterial infection may develop in the skin rash. Secondary infection of lesions of scabies due to nephritogenic streptococci may complicate the rash leading to post streptococcal glomerulonephritis.

Scabies Diagnosis

Scabies Clinical grounds: Scabies should be considered on the basis of clinical presentation and history. Diagnosis can be made in patients with itching and symmetrical skin lesions in characteristic distribution/locations. It may be obvious if there is a history of household/close contact with an affected patient.

Scabies Confirmation of scabies: It is by identifying the scabietic burrow and visualizing the mite. Burrows should be unroofed with a sterile needle or scalpel blade.

The skin scrapings of a lesion should be examined microscopically (by a potassium hydroxide preparation) for the mite and/or its eggs and its fecal pellets. Microscopic examination of clear adhesive tape lifted from lesions and skin biopsy also may be useful for diagnosis.

Scabies Dermoscopy: The characteristic finding is a dark and triangular shape that represents the head of the mite within a burrow (“delta wing” sign).

Question 41. Write a short note on crusted scabies/Norwegian scabies.
Answer:

Norwegian Scabies Crusted or Norwegian Scabies

• Crusted scabies, Boeck scabies, keratotic scabies, or Norwegian scabies is clinical variant of scabies characterized by hyperinflation (huge numbers) of Sarcoptes scabiei mites in the skin.
• It is named Norwegian scabies because of its initial description in Norwegian patients with leprosy.
• Predisposing conditions: Patients are highly infectious. The number of mites rapidly increases (hyperinflation) due to impaired immune response, lack of pruritus or patients with neurological disorders with a physical inability to scratch.
• Disorders predisposing to crusted scabies are listed in Table 22.16. It may be associated with HLA-A11. Transmission through fomites can occur because mites survive on the sloughed skin in the environment.
• Clinical features: The patient presents with marked thickening and crusting of the skin (hyperkeratotic crusted lesions) particulars on the hands.
• However, the entire body including the face and scalp is often involved. Nails often show hyperkeratosis. Pruritus is minimal or absent.

Disorders predisposing to crusted scabies are shown.

Question 42. Discuss the management of scabies/drugs used to treat scabies.
Answer:

Treatment

Principles of Scabies Treatment

• Topical treatment of the patient and all asymptomatic close contacts (family members/physical contacts) should be done simultaneously to ensure eradication.
• Include a scabicidal and a keratolytic in the treatment.
• To avoid reinfection, washing, or cleaning of recently worn clothes (including underclothing) and bed linen (preferably at 60°C) is recommended.

Principles of Scabies Treatment Topical Treatment

• Areas of application: Scabicides are applied thinly and thoroughly to all over the skin below the neck (including the genitalia, palms, and soles, and under the nails). Reapply topical scabicide to the hands, if the patient washed it during the treatment period.
• Duration of treatment: Usually, effectively treated scabies infestations become noninfectious within a day. However, even after successful treatment, pruritus/itching and rash may remain even up to 4 weeks. Unnecessary retreatment may cause contact dermatitis.
• Repetition of application: Topical application should be repeated after 1 week.
  Topical Scabicide

Principles of Scabies Treatment These include

1. precipitated sulfur 2–10% in petrolatum,
2. benzyl benzoate 10–25%,
3. crotamiton 10%,
4. Lindane (gamma benzene hexachloride) 1%,
5. permethrin 5%, and
6. malathion 0.5%.

Principles of Scabies Treatment Oral Therapy

Principles of Scabies Treatment Ivermectin

Principles of Scabies Treatment Dose:

• A single oral dose of 200 µg/kg in otherwise healthy individuals and side effects are rare.
• Two doses of oral ivermectin (200 μg/kg, as 2 doses 2 weeks apart) are easy to use and as effective as a topical therapy. Two doses are indicated in crusted scabies or Norwegian scabies. The toxic effects with two doses are insignificant. Oral antihistamines can alleviate the hypersensitivity response.

Lice Infection

Question 43. Write a short essay/note on pediculosis.
Answer:

Lice are blood-sucking ectoparasites and can infest humans in three ways:

1. Head lice (pediculosis capitis):

• Infestation with the head louse, Pediculus humanus capitis, is common worldwide.
• Age and gender: Predominantly affects children and more common in females.
• Spread:
  • It is highly contagious and spread by direct head-to-head contact and is associated with overcrowding.
  • It may be indirectly spread through hats, clothes, or pillow covers.
• Clinical presentation: Head lice usually present with scalp itch that leads to scratching, scalp excoriations, secondary infection (an important cause of impetigo), and cervical lymphadenopathy. Itching may produce sleep disturbances and difficulties in concentration and the affected children may perform poorly in school.
• Diagnosis:
  • Confirmed by identifying the living louse or nymph or empty egg cases (“nits” look like whitish shells stuck to the hair shaft on the scalp and are difficult to dislodge)

Lice Infection Treatment

• Apply malathion or permethrin or carbaryl or phenothrin in lotion or aqueous formulations, twice at an interval of 7–10 days (with a contact time of 12 hours). If treatment with one fails, a different insecticide is used for the next course. Rotational treatments within a community can avoid resistance. Treatment is usually repeated after 7 days.
• Regular “wet-combing” (physical removal of live lice by regular combing of conditioned wet hair, metal nit combs may help remove the eggs) is less effective than pharmacological applications.
• Apply Vaseline to eyelashes/brows twice daily for at least a fortnight.
• Resistant cases: Use oral ivermectin (400 μg/kg as two doses 1 week apart)
• Treatment of secondary bacterial infection if present

2. Body lice (Pediculosis corporis)

• Body lice are ectoparasites similar to head lice but they live on clothing (e.g., seams), and feed on the skin.
• Predisposing factors include poor hygiene, poverty, neglect, and overcrowded conditions. It is rare in developed countries (except for the homeless and vagrants).
• Spread: By direct contact or sharing infested clothing. The lice and eggs are commonly found on the clothing but are rarely observed on the skin of the patient.
• Clinical presentation: It presents with itch, excoriations, and secondary infection. Sometimes, there may be
  postinflammatory hyperpigmentation of the skin.

Lice Infection Treatment: By malathion or permethrin. Dry cleaning and high-temperature washing or insecticide treatment for the clothes is helpful.

3. Pubic lice (Crab lice or Phthiriasis pubis):

• Pubic louse (Phthirus pubis) is a bloodsucking insect that attaches tightly to the pubic hair.
• Mode of transmission: Usually, it is sexually acquired (direct contact) and transferred only by close bodily contact.
• The lice lay their eggs (nits) at hair bases and usually hatch within a week.
• Clinical presentation: It may be asymptomatic or present with severe itching, especially at night. It usually infests public hair and occasionally other hairy areas (eyebrows, eyelashes, and the beard). Lice can be seen near the base of the hair with eggs.

Lice Infection Treatment: Similar to head lice and the treatment of choice is malathion or carbaryl in an aqueous base. They are applied on two occasions to the whole body because it can also infest body hair. All sexual contacts (patient’s partner) should also be treated.

Patients should be screened for other sexually transmitted diseases. Infestation of the eyelashes and eyebrows is treated with an application of white soft paraffin three times daily for 1–2 weeks.

Sexually Transmitted Infections

Sexually transmitted diseases (STDs) are a group of communicable diseases that are transmitted predominantly by sexual contact and caused by a wide range of bacterial, viral, protozoal, and fungal agents and ectoparasites.

Gonorrhea

Question 44. Write a short note on gonorrhea/acute gonococcal urethritis.
Answer:

Gonorrhea Definition: Gonorrhea is a sexually transmitted infection (STI) due to the gram-negative diplococcus, Neisseria gonorrhoeae. It commonly infects columnar epithelium in the lower genital tract (cervicitis and urethritis), rectum (proctitis), and eye (conjunctivitis).

Gonorrhea Mode of transmission: Genital–genital, genital–anorectal, or orogenital or coronal contact or from mother-to-child transmission during delivery

Incubation period: Usually 2–10 days following exposure

Gonorrhea Clinical Features

• Gonococcal infections in men: Acute urethritis is the most common clinical manifestation and presents with urethral discharge and dysuria usually without urinary frequency or urgency. On examination, the urethra shows mucopurulent discharge that may be accompanied by erythema of the urethral meatus.
• Gonococcal infections in women: Gonococcal cervicitis and vaginitis present with symptoms related to endocervical and urethral infection and include scant vaginal discharge and dysuria. Gonococci may infect the urethra, paraurethral glands/ducts, and Bartholin’s glands/ducts. It may be asymptomatic in up to 80% of women.
• Anorectal and pharyngeal gonorrhea are usually asymptomatic.
• Ocular gonorrhea: Gonococcal conjunctivitis is uncommon. It may present with purulent discharge from the eye(s), inflammation of the conjunctivae and edema of the eyelids, pain, and photophobia.
• Gonococcal ophthalmia neonatorum also presents with purulent conjunctivitis and edema of the eyelids. Conjunctivitis must be treated early to prevent corneal damage.
• Disseminated gonococcal infection (DGI): Dissemination can result in gonococcal bacteremia and is rare and develops in women with asymptomatic genital infections.
• Symptoms include arthritis of one or more joints (asymmetric and migratory), pustular skin lesions, fever, and tenosynovitis. Gonococcal endocarditis or meningitis may rarely occur.
• Acute perihepatitis (Fitz–Hugh–Curtis syndrome) is a rare complication of PID and is thought to occur through direct extension of N. gonorrhoeae from the fallopian tube to the liver capsule and peritoneum along the paracolic gutters. Patients present with sharp, pleuritic right upper quadrant pain.

Gonorrhea Diagnosis

• Gram staining and culture of urethral exudates, genital, rectal, pharyngeal, or ocular secretions show gram-negative intracellular gonococci and diplococci.
• Sterile pyuria: Urine may show polymorphonuclear leukocytes with a negative urine culture report.
• Nucleic acid probe tests: Nucleic acid amplification tests (NAATs) are more sensitive than culture. They can be performed on urine samples, and swabs from the endocervix, urethra, rectum, and pharynx.
• Direct antigen detection by fluorescein-conjugated monoclonal antibodies and direct fluorescence microscopy
• Enzyme-linked immunoassays for the detection of gonococcal antigen
• Blood cultures in disseminated disease.

Gonorrhea Complications

• If untreated infection can develop the following complications:
• In females: It causes pelvic inflammatory disease PID (pelvic inflammatory disease). Local complications such as endometritis, salpingitis, tubo-ovarian abscess, bartholinitis, peritonitis, and perihepatitis
• In male patients: Periurethritis, epididymitis epididymo-orchitis, and prostatitis
• Newborns: Ophthalmia neonatorum in newborns

Gonorrhea Treatment of Gonorrhea

• One of the following regimens is recommended at present:
  • Cefixime 400 mg orally (single dose)
  • Ceftriaxone 250 mg intramuscularly (single dose)
  • Spectinomycin 2 g intramuscularly (single dose)
• If quinolone and azithromycin resistance is not a problem:
  • Ciprofloxacin 500 mg orally (single dose)
  • Ofloxacin 400 mg orally (single dose)
  • Levofloxacin 250 mg orally (single dose)
  • Azithromycin 2 g orally (single dose)
• For epididymal orchitis, doxycycline 100 mg twice daily for 14 days along with one dose of ceftriaxone or ciprofloxacin

Nongonococcal Urethritis

Question 45. List the etiology and drugs used in nongonococcal urethritis.
Answer:

Etiology

Nongonococcal Urethritis Signs and Symptoms

Symptoms and signs of gonococcal urethritis and nongonococcal urethritis are similar but differ significantly in severity.

Nongonococcal Urethritis Diagnosis

• Gram staining of discharge or sediment of first voided urine (symptomatic/asymptomatic)
• Direct fluorescence assay
• Enzyme immunoassay
• Hybridization assay
• Nucleic acid amplification tests

Nongonococcal Urethritis Treatment

STD treatment guidelines from the CDC, 2010 and the WHO recommends:

• Doxycycline 100 mg twice daily for 7 days, or
• Azithromycin 1 g orally

Nongonococcal Urethritis Alternatives

• Erythromycin base 500 mg four times for 7 days, or
• Ofloxacin 300 mg twice daily for 7 days, or
• Levofloxacin 500 mg once daily for 7 days

Nongonococcal Urethritis General Features

• All sex partners in the last 60 days should be evaluated and treated
• Sexual abstinence till completion of treatment
• Patients should be reviewed 2–3 weeks after treatment to confirm the resolution of symptoms and treatment of sexual contacts
• Patients should be checked for other STIs including syphilis and HIV. The results of tests should be checked during the review.

Chancroid

Question 46. Write a short essay/note on clinical features and treatment of chancroid.
Answer:

• Chancroid or soft chancre is an acute sexually transmitted infection caused by Haemophilus ducreyi. It is characterized by painful genital ulcerations and inguinal adenitis.
• Genital ulceration in the chancroid increases the efficiency of transmission and the degree of susceptibility to HIV in infection.
• Coinfection with Treponema pallidum and herpes simplex is observed in 10% of cases.

Chancroid Clinical Features

• Incubation period: Usually 3–10 days
• Infection is acquired due to a break in the epithelium during sexual contact with an infected individual
• Lesions in the external genitalia:
  • Sites of lesions: Prepuce and frenulum in men and vaginal entrance and the perineum in women. At the site of inoculation (the external genitalia), an initial erythematous papule appears, which then breaks down within 2–3 days into a classic chancroidal ulcer.

Chancroid Characteristics of ulcer: The chancroid ulcer is superficial, circumscribed, and painful. Ulcers have ragged and undermined edges, and necrotic base bleeds easily and are generally not indurated. An ulcer may be single. If multiple, they may merge to form a giant serpiginous ulcer.

Chancroid Lymphadenopathy: About 50% of patients develop enlarged, painful, and tender inguinal lymph nodes (usually unilateral). The involved nodes become matted and progress to form large unilocular buboes, which is suppurate.

Chancroid Diagnosis

• It is based on the microscopic identification and culture isolation of Haemophilus ducreyi in scrapings from ulcers or pus from bubo.
• Polymerase chain reaction (PCR) technique not commercially available
• Detection of antibodies to H. ducreyi using EIA may be useful.

Chancroid Treatment of chancroid

Sex partners of chancroid patients should be examined and treated if they had sexual contact with the patient during the 10 days preceding the patient’s onset of symptoms. This is regardless of whether they have symptoms of the disease or not.

Chancroid Treatment options for chancroid.

• Azithromycin, 1 g orally, as a single dose, or
• Ceftriaxone, 250 mg by intramuscular injection as a single dose, or
• Ciprofloxacin, 500 mg orally, twice daily for 3 days, or
• Erythromycin base, 500 mg orally 4 times daily for 7 days

Chancroid Chlamydial Infections

Chlamydial infections may be asymptomatic or cause:

• In male: Urethritis, epididymitis, and prostatitis. Untreated infection can cause infertility and reactive arthritis.
• In females: Cervicitis and salpingitis. Most of the infected females are asymptomatic and are likely to develop complications such as PID, infertility, or ectopic pregnancy.

Lymphogranuloma Venereum

Question 47. Write a short note on lymphogranuloma venereum (LGV).
Answer:

It is a sexually transmitted disease caused by Chlamydia trachomatis (types LGV 1, 2, and 3).

Lymphogranuloma Venereum Clinical Features

Lymphogranuloma Venereum Incubation period: 3–30 days.

Lymphogranuloma Venereum Stages: Three characteristic stages

1. Primary genital lesion: LGV starts as an asymptomatic small painless papule at the site of inoculation (external genitalia) and tends to ulcerate.
2. Regional lymphadenopathy: Within a few days to weeks, the ulcers heal and regional lymphadenopathy (usually
   unilateral) develops. The lymph nodes are initially discrete painful and fied and the overlying skin appears dusky and erythematous.
3. Buboes: Later in the course, the lymph nodes may become matted, fluctuant (buboes), and rupture. The overlying skin becomes thinned, inflamed, and fied. Finally, multiple draining fistulae may occur. Extensive enlargement of inguinal lymph nodes above and below the inguinal ligament (“groove sign”) can develop.

Lymphogranuloma Venereum Other features:

• Acute LGV can also cause proctitis with perirectal abscesses, which may resemble anorectal Crohn’s disease.
• Chronic phase: Chronic infection may produce extensive scarring, abscess and sinus formation. The destruction of local lymph nodes can produce lymphedema of the genitalia.
• Constitutional symptoms: These include fever, chills, headache, anorexia, meningismus, myalgia, and arthralgia.

Lymphogranuloma Venereum Diagnosis

• Detection of nucleic acid (DNA): Direct immunofluorescent antibody and nucleic acid amplification tests are positive, which should be confirmed by real-time PCR for LGV-specific DNA.
• Isolation of the LGV (L1–3 serotypes) strain of Chlamydia: Tissue culture from swab obtained from ulcer-aspirated bubo pus, rectum, urethra, endocervix, or from other infected tissue is the most specific test; however, sensitivity is only 75–85%.
• Serological tests: Microimmunofluorescence (micro-IF) test and complement fixation test (CF) to detect antibodies
• Frei skin test is not useful.

Lymphogranuloma Venereum Treatment

• Early treatment is necessary to prevent the chronic phase.
• Fluctuant buboes should be aspirated with a syringe and needle.
• Surgical drainage or reconstructive surgery may be sometimes needed

Treatment options for lymphogranuloma venereum.

• Doxycycline, 100 mg orally, twice daily for 14 days, or
• Erythromycin, 500 mg orally, 4 times daily for 14 days, or
• Tetracycline, 500 mg orally, 4 times daily for 14 days

Granuloma Inguinale (Donovanosis)

Question 48. Write short note on granuloma inguinale (donovanosis).
Answer:

Granuloma inguinale is a genital ulcerative disease caused due to intracellular gram-negative bacterium Klebsiella granulomatis formerly known as Calymmatobacterium granulomatis (Donovan bodies).

Granuloma Inguinale (Donovanosis) Incubation period: 3–40 days

Granuloma Inguinale (Donovanosis) Clinical Features (Genital Lesions)

• Painless and progressive ulcerative lesions without regional lymphadenopathy
• Genital lesions are highly vascular, produce “beefy red appearance”, and bleed easily on touch. However, it can also produce hypertrophic granulomatous, necrotic, or sclerotic lesions.

Granuloma Inguinale (Donovanosis) Diagnosis

Microscopy examination of material from the lesion (tissue crush preparation or biopsy) shows dark-staining intracellular bipolar-staining Donovan bodies. The causative organism is difficult to culture.

Granuloma Inguinale (Donovanosis) Treatment

• Treatment will prevent the progression of lesions. Treatment should be continued until all lesions have been completely epithelialized.
• Treatment with antibiotics is needed for at least 3 weeks. Effective regimens are presented.

Granuloma Inguinale (Donovanosis) Treatment options for granuloma inguinale.

• Azithromycin, 1 g orally on the 1st day, then 500 mg orally, once a day, or
• Doxycycline, 100 mg orally, twice daily, or
• Erythromycin, 500 mg orally, 4 times daily, or
• Tetracycline, 500 mg orally, 4 times daily, or
• Trimethoprim 80 mg/sulfamethoxazole 400 mg, 2 tablets orally, twice daily

Syphilis

Question 49. Classify syphilis based on the presentation and clinical manifestations.
Answer:

Syphilis (lues) is a chronic, systemic infection caused by spirochete Treponema pallidum, which is usually sexually transmitted.

Spirochetes are gram-negative and slender corkscrew-shaped.

Syphilis Source of Infection

Contact with an open infectious lesion of primary or secondary syphilis. Lesions in the mucous membranes or skin of the genital organs, rectum, mouth, fingers, or nipples. These lesions include chancre, mucous patch, skin rash, or condylomata lata.

Syphilis Mode of Transmission

• Sexual contact: It is the usual mode of spread.
• Transplacental transmission: From the mother with active disease to the fetus (during pregnancy) with congenital syphilis
• Blood transfusion
• Direct contact with the open lesion is a rare mode of transmission.
• Transmission from a mother to her fetus and rarely by blood transfusion is possible for several years following infection.
• Treponema pallidum can penetrate intact mucous membranes or abraded skin rapidly and gain entry into the lymphatics and bloodstream and produce systemic infection.

Syphilis Classification

Syphilis Acquired Syphilis

Syphilis Primary syphilis

Syphilis Primary chancre: It is the classical lesion of primary syphilis.

• Location: The primary chancre develops at the site of inoculation.
  • In males: Penis or scrotum in males (in heterosexual) and in homosexual males, it may occur in the anal canal, rectum, fingers, or within the mouth.
  • In females: The cervix, vulva, and vaginal wall
• The primary chancre is a single, firm, non-tender (painless), slightly raised, red papule (chancre) up to several centimeters in diameter. It rapidly becomes eroded to create a clean-based shallow ulcer. Because of the induration surrounding the ulcer, it is designated as a hard chancre.

Syphilis Regional lymphadenitis: Usually accompanies the primary chancre within 1 week of the onset of the lesion.

• The lymph nodes are firm, rubbery, mobile, nonsuppurative, painless, and non-tender.
• Chancres on external genitalia and anus produce bilateral inguinal lymphadenopathy, whereas those on cervix and vagina cause iliac or perirectal lymphadenopathy.

Syphilis Fate: Even without therapy, the primary chancre heals within 4–6 weeks, but the lymphadenopathy may persist for months.

• Primary syphilis in HIV-positive patients is often asymptomatic and they frequently present with secondary or latent syphilis.

Syphilis Secondary syphilis

Secondary syphilis develops 4–10 weeks after the primary chancre in approximately 75% of untreated patients. Its manifestations are due to systemic spread and proliferation of the spirochetes within the skin and mucocutaneous tissues.

It starts with symptoms of generalized infection such as malaise, sore throat, headache, low-grade fever, and arthralgia.

Syphilis Lesions

Syphilis Mucocutaneous lesions: These are painless and superficial lesions and contain spirochetes and are infectious.

• Skin rashes (75%): They begin as discrete red-brown macules <5 mm in diameter. They are generalized symmetrical and nonirritable but more frequent on the trunk and proximal limbs.
• These macular lesions may progress to scaly/pustular/ annular or necrotic ulcers, which frequently involve the palms and soles. The lesions are initially red, changing to a “gun–metal” gray as they resolve.
• Condylomata lata (10%) (Fig. 23.35B): These are broad-based, moist, pink, or gray–white, elevated plaques (papules coalescing to plaques), highly infectious containing numerous spirochetes.
• They are seen in moist, warm, intertriginous areas of the skin, such as the anogenital region (perineum, vulva, and scrotum), inner thighs, and axillae.
• Mucosal lesions (30%): These usually occur in the mucous membranes of the oral cavity (lip, oral mucosa, tongue, palate, and pharynx) or vulva, vagina, or glans penis as silvery-gray superficial mucosal erosions.
• They are surrounded by a red serpiginous periphery and are usually painless. Rarely, they may coalesce to produce characteristic “snail track” ulcers in the mouth.
• These lesions contain numerous T. pallidum and are the highly infectious. Microscopy: Similar to primary chancre, infiltration by plasma cells and endarteritis obliterans.

Syphilis Generalized painless lymphadenopathy: Generalized, firm non-tender lymphadenopathy (shotty) occurs in about 50% of patients. They involve, especially epitrochlear nodes and show plenty of spirochetes.

Mild fever, malaise, and weight loss are common in secondary syphilis, which may last for several weeks. The lesions subside even without treatment.

Syphilis Less common manifestations include meningitis, cranial nerve palsies, anterior or posterior uveitis, hepatitis, gastritis, glomerulonephritis (proteinuria, nephrotic syndrome, or hemorrhagic glomerulonephritis), or arthritis and periostitis.

Syphilis Latent syphilis

Without treatment, the clinical manifestations of secondary syphilis will resolve over 3–12 weeks. In an untreated (about 30%) patient during this phase, there is no evidence of clinical disease but it shows the presence of positive syphilis serology or the diagnostic cerebrospinal fluid (CSF) abnormalities of neurosyphilis. This is known as latent syphilis and is divided into:

• Early latency (within 1 year of infection): During this period, syphilis may be transmitted sexually.
• Late latency (begins at 1 year of infection): During this period, the patient is no longer sexually infectious. Pregnant women with latent syphilis may infect the fetus in utero.

Syphilis Late (tertiary) syphilis

• Late latent syphilis:
  • This phase may persist for many years or for life.
  • No symptoms or signs of syphilis
  • More than 60% of patients suffer little or no ill health even without treatment.
• Benign tertiary (gummatous) syphilis:
  • It is called benign because of its response to therapy rather than its clinical manifestations.
  • It may develop after 3–10 years after initial infection.
  • Structures involved: Skin (frequently at sites of trauma as nodules or ulcers), mucous membranes (mouth, pharynx, larynx, or nasal septum appears as punched-out ulcers), bone (Example: skull, tibia, fibula, and clavicle) muscle, or viscera (Example: liver hepar lobatum and spleen).
  • Characteristic feature: It is a chronic granulomatous (sometimes ulcerating) lesion called a gumma, which may be single or multiple.
  • Consequences: Healing with scar formation may damage the function of the structure involved.
• Quaternary syphilis: Neurosyphilis and cardiovascular syphilis may coexist and are sometimes called quaternary syphilis.
• Cardiovascular syphilis:
  • It may present many years after the initial infection.
  • Most frequently involves the aorta (the ascending aorta aortic valve and/or the coronary ostia, the aortic arch) and is known as syphilitic aortitis
  • Clinical features include angina, features of aortic incompetence, and aortic aneurysm.
• Neurosyphilis (discussed in Chapter 15).

Congenital Syphilis

Question 50. Write a short note on congenital syphilis.
Answer:

• Transplacental transmission: T. pallidum can cross the placenta and spread from the infected mother to the fetus (during pregnancy).
• Transmission occurs when the mother is suffering from primary or secondary syphilis (when the spirochetes are abundant). Because routine serologic testing for syphilis is done in all pregnancies, congenital syphilis is rare.

Congenital Syphilis Manifestations

It can be divided into:

• Intrauterine death and perinatal death
• Early (infantile) congenital syphilis: It manifests within the first 2 years of life and often manifested by nasal discharge (rhinitis) and congestion (snuffles). They resemble features of secondary syphilis.
  • A desquamating or bullous eruption/rash can lead to epidermal sloughing of the skin, mainly in the hands, feet, around the mouth, and anus. It also may show condyloma lata.
  • Skeletal abnormalities: Syphilitic osteochondritis (inflammation of bone and cartilage is more distinctive in the nose and produces characteristic saddle nose deformity); syphilitic periostitis (involves the tibia and leads to anterior bowing or saber shin)
  • Other organs involved are the liver (diffuse fibrosis) and lung (airless-pneumonia alba

Congenital Syphilis Late (tardive) congenital syphilis:

• Manifests 2 years after birth, and about 50% of untreated children with neonatal syphilis will develop late
  manifestations and take the form of “stigmata” relating to early damage to developing structures, particularly teeth and long bones.
• Distinctive manifestations in Hutchinson’s triad are

1. interstitial keratitis,
2. Hutchinson’s teeth, and eighth nerve deafness. Other features include Clutton’s joints, neurosyphilis, gummatous periostitis, destruction of palate, and nasal septum. Cardiovascular involvement is rare. Stigmata of congenital syphilis are listed.

Laboratory Diagnosis

Question 51. Write a short note/essay on
(or)Tests for diagnosis of syphilis
Serological tests for syphilis
Venereal Diseases Research Laboratory (VDRL) test
Answer:

Laboratory Diagnosis Demonstration of Treponema Pallidum

• Dark-field microscopy: Most sensitive and specific method is identification in serum collected from primary chancres, or from moist or eroded mucous lesions in secondary syphilis by dark-field microscopy.
• It shows the drifting rotary motion (corkscrew) of Treponema pallidum. Patients with either primary or secondary diseases are highly infectious.
• Direct fluorescent antibody T. pallidum (DFA-TP) test: In fixed smears from the chancre, it is important for the diagnosis of primary syphilis.
• Microscopic demonstration of Treponema pallidum in tissues stained by appropriate stains and PCR are also useful.

Laboratory Diagnosis Serological Tests

• Nontreponemal antibody (nonspecific) tests: These tests measure antibodies to cardiolipin, a phospholipid presents in both host tissues and T. pallidum.
• These tests include:
• Venereal Diseases Research Laboratory (VDRL) test
• Rapid plasma reagin (RPR) test
• Treponemal (specific) antibody tests: They measure antibodies, which react with T. pallidum.
• Significance
  • Used for confirmation. They are highly specific for treponemal disease. However, they do not differentiate between syphilis and other treponemal infection (Example: as yaws).
  • In most of the patients, these tests usually remain positive for life, regardless of treatment or disease activity. However, 15–25% of patients treated in the primary stage become nonreactive after 2–3 years.
  • Various tests include:
    • Treponemal antigen-based enzyme immunoassay (EIA) for IgG and IgM
    • T. pallidum hemagglutination assay (TPHA)
    • T. pallidum particle agglutination assay (TPPA)
    • Fluorescent treponemal antibody absorption (FTA-ABS) test

Laboratory Diagnosis Examination of CSF: In benign tertiary and cardiovascular syphilis, CSF should be examined because of the coexistence
of asymptomatic neurological disease. CSF should be examined in neurosyphilis and in both early and late congenital syphilis.

Laboratory Diagnosis Other tests: Chest X-ray, electrocardiogram (ECG), and echocardiogram are necessary in cardiovascular syphilis. A biopsy may be necessary to diagnose gumma.

Question 52. Enumerate the indications and describe the pharmacology, administration, and adverse reaction of pharmacotherapies for syphilis.
Answer:

Pharmacotherapies for Syphilis Management

• Patients allergic to penicillin: In primary, secondary, and early latent syphilis, these patients should be given tetracycline or doxycycline for 2 weeks, and in late latent syphilis, it should be given for 4 weeks.
• Ceftriaxone: It may be given in the dose of 1 g once a day for 10–14 days.
• Azithromycin: Single dose of 2 g is also effective except in homosexual men and during pregnancy.
• Response to treatment is considered as satisfactory if there is a four-fold decrease in nontreponemal titers at 3–6 months in all stages of syphilis.
• Neurosyphilis: It should be followed up with lumbar puncture and evaluation of CSF every 6 months until the cell count is normal. If after 6 months the cell count is not decreased, retreatment should be given.

Pharmacotherapies for syphilis  Treatment reactions

• Anaphylaxis: Penicillin is a common cause.
• Jarisch Herxheimer reaction:
  • Treatment of syphilitic patients having a high bacterial load by antibiotics can cause a massive
    release of endotoxins, and cytokine causing Jarisch–Herxheimer reaction.
  • Jarisch–Herxheimer reaction is an acute febrile reaction that follows (about 8 hours after
    the first injection) any therapy for syphilis. It is characterized by headache, myalgia, malaise, mild fever, rigors, and other symptoms that usually resolve within the first 24 hours.
  • It is common in early syphilis and rare in late syphilis.
  • It may induce fetal distress or premature labor in pregnancy. This concern should not prevent or delay therapy. It may be severe and worsen the clinical manifestations of cardiovascular or neurosyphilis.
  • Penicillin should not be withheld because of the Jarisch–Herxheimer reaction. Because it is not
    dose-dependent and there is no point in giving a smaller dose.
  • Prednisolone 10–20 mg orally three times daily for 3 days given for 24 hours prior to therapy may prevent the reaction.

Pharmacotherapies for Syphilis Approach To A Case Of Genital Ulcer [Genital Ulcer Disease (Gud)]

Pharmacotherapies for syphilis  Definition: Genital ulcer is defined as ulcerative, erosive, pustular, or vesicular lesions on the genitalia with or without lymphadenopathy.

Etiology

Features and differential diagnoses of genital ulcer disease are presented.