📚 Question Bank

Stevens-Johnson syndrome (SJS) involves less than 10 of body surface area (BSA).

Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) are severe mucocutaneous reactions, usually to drugs, characterized by blistering and epithelial sloughing. The two terms describe phenotypes within a severity spectrum, where SJS is the less extensive form and TEN is the more extensive.

Based on the type of cutaneous lesion and extent of maximal epidermal detachment, the disease is classified as:

Disease

SJS

Overlap SJS-TE N

TEN with spots

TEN without sp ots

Epidermal detachment

<10

10-30

>30

>30 (large sheets of epider mal loss)

Purpuric macules and atypica l target lesions

Present Present

Present Absent

The image below shows SJS in the early stages with mucosal involvement.

The image shows atypical target lesions with 2 zones. The rash and flaccid blisters affecting the back (epidermal detachment lt;10 BSA), conjunctivitis, cheilitis (mucosal involvement), with the history of drug intake (triggering factor) favor a diagnosis of Stevens-Johnson syndrome.

Option A: Fixed drug eruptions present up to 8 hours of drug intake. These are erythematous lesions that heal with hyperpigmentation. Mucosal involvement is rare.

Option B: Erythema multiforme shows typical target or raised atypical target lesions, that develop over few days and resolve in 2 to 3 weeks. Mucosal involvement is rare if the trigger is a drug.

Option D: In toxic epidermal necrolysis, gt;30 of body surface area is involved. Diffuse generalized epidermal detachment is seen with extensive mucosal involvement.

Blistering and peeling involving greater than 30 of the body surface area points to the diagnosis of toxic epidermal necrolysis (TEN). TEN is primarily druginduced, with a culprit drug being demonstrated in approximately 85 of cases.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are both severe mucocutaneous reactions, characterized by blistering and epithelial sloughing. The two terms describe phenotypes within a severity spectrum, where SJS is the less extensive form and TEN is the more extensive

Common drugs that can cause SJS/TEN are:

• Allopurinol
• NSAIDs- oxicam group
• Anti-epileptics - phenobarbital, phenytoin, carbamazepine, lamotrigine
• Antibiotics - penicillins, cephalosporins, sulfamethoxazole, sulfasalazine, nevirapine

Disease

SJS

Overlap SJS-TE N

TEN with spots

TEN without sp ots

Epidermal detachment

<10

10–30

>30

>30 (large sheets of epider mal loss)

Purpuric macules and atypica l target lesions

Present Present

Present Absent

As more than 30 of the body surface is involved, the diagnosis is toxic epidermal necrolysis (TEN). SJS/TEN is primarily a druginduced phenomenon, with a culprit drug being demonstrated in approximately 85 of cases.

Common drugs that can cause SJS/TEN are:

• Allopurinol
• NSAIDs - oxicam group
• Anti-epileptics - phenobarbital, phenytoin, carbamazepine, lamotrigine
• Antibiotics - penicillins, cephalosporins, sulfamethoxazole, sulfasalazine, nevirapine

In 15 of the cases, where the drug cannot be identified, especially in children, appear to be triggered by infections, most notably by Mycoplasma pneumoniae.

Note: FDA recommends genotyping before starting carbamazepine, as HLA B1502 allele which is seen in increased frequencies among Asians is implicated in carbamazepine induced SJS/TEN.

The characteristic lesion healing with hyperpigmentation following drug intake is consistent with fixed drug eruption. NSAIDs are the most commonly implicated drug.

Fixed drug eruption (FDE) is a cutaneous adverse drug reaction characterized by recurrent welldefined lesions occurring at the same sites each time the offending drug is taken. It typically presents 30 min to 8 h after drug exposure.

The most common drugs that act as triggers are:

• NSAIDs (25)
• Paracetamol (15)
• Cotrimoxazole
• Tetracyclines

FDE is a form of classical delayedtype hypersensitivity reaction.

Typically, FDE presents as a sharply defined, round, or oval erythematous and oedematous plaque, which evolves to become dusky, violaceous, and occasionally vesicular or bullous lesions. Lesions are usually solitary or few in number.

Commonly affected sites include the lips, genitals, palms, and soles; 5 of cases may have an exclusive mucosal involvement. Overall, the most common site involved is the genitalia.

The majority of FDE is selflimiting with an excellent prognosis.

Note: The generalized bullous form of FDE should be differentiated from toxic epidermal necrolysis by prior similar history, absence of target lesions, and no involvement of mucosal surfaces.

Glans penis is the best answer among the given options. Fixed drug eruptions(FDE) can occur anywhere in the body. However, 50 of FDE occurs in the genital and oral mucosa. The other common sites are palms and soles.

Drugspecific clinical patterns have been reported. These include the following:

• NSAIDinduced FDE - genitals and lips
• Tetracycline and trimethoprim/sulfamethoxazoleinduced FDE - genitals
• Metamizoleinduced FDE - trunk and extremities
• Carbocysteineinduced FDE - face

The image below shows hyperpigmentation on the glans penis- healed fixed drug eruption.

Erythema nodosum (EN) is a cutaneous reactive septal panniculitis with no vasculitis to a variety of stimuli.

It is believed to be a type IV delayed hypersensitivity reaction to various antigens including medicines.

It presents with symmetrical, erythematous, and tender subcutaneous nodules or plaques which are typically distributed over the anterior aspect of the limbs. Over a few days, these lesions become purplish before finally turning brown. Ulceration never occurs.

The clinical course is selflimiting following drug withdrawal and usually resolves within 2–4 weeks.

The description is classical of erythema nodosum. They are not seen in chronic pancreatitis. Aetiological factors in erythema nodosum:

• NO- Idiopathic, pregnancy
• DO-Drugs - oral contraceptives, hormonal replacement therapy, sulphonamides, and penicillin
• S- Sarcoidosis, Sweet syndrome, SLE, RA, Reiter's syndrome
• U- Ulcerative colitis, Crohn's disease, Behcet's disease
• M- Malignancy, and microbiology( Infections - Group A β-hemolytic streptococcus
• infection

(most common), brucella, toxoplasmosis, CMV, E.coli, yersinia, tuberculosis) The image below shows erythema nodosum.

The most commonly affected internal organ in DRESS syndrome is the liver. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is an idiosyncratic multisystem drug hypersensitivity disorder.

DRESS is characterized by an urticarial papular rash suspected to be drug induced, accompanied by a fever, lymphadenopathy and systemic symptoms referring to derangement of the function of at least one organ system, and haematological abnormalities.

The latency period from drug intake to the appearance of symptoms is 2–6 weeks. The most commonly implicated drugs in DRESS syndrome are:

• Antiepileptics – carbamazepine, phenytoin, lamotrigine
• Antibiotics – vancomycin, amoxicillin, minocycline, piperacillin-tazobactam
• Sulpha drugs – sulphasalazine, dapsone, sulphadiazine
• Furosemide
• Omeprazole
• Ibuprofen

The most severe and lifethreatening complication of DRESS is fulminant liver failure.

The majority of patients with DRESS will recover fully, following withdrawal of the culprit drug and management of the acute episode with systemic corticosteroid therapy, IVIG therapy and other supportive measures.

Note: DRESS syndrome is now declared as an adverse effect of the commonly used painkiller Mefenamic acid.

Lyell's syndrome is another name for toxic epidermal necrolysis, which is characterized by erosions of more than 30 of body surface area.

Based on the type of cutaneous lesion and extent of maximal epidermal detachment, the disease is classified as:

Disease

SJS

Overlap SJS-TE N

TEN with spots

TEN without sp ots

Epidermal detachment

<10

10-30

>30

>30 (large sheets of epider mal loss)

Purpuric macules and atypica l target lesions

Present Present

Present Absent

The image shows a papulosquamous lesion. Basal cell carcinoma does not cause papulosquamous lesions.

Papulosquamous disorders are diseases that present with papules/plaque with scaling. They include:

• Lichen planus
• Psoriasis
• Parapsoriasis
• Pityriasis rubra pilaris
• Pityriasis rosea
• Seborrheic dermatitis
• Secondary syphilis
• Drug reactions
• Reiter’s disease
• Eczema
• Neoplasms (mycosis fungoides, squamous cell carcinoma, Bowen’s disease)
• Tinea infection

The skin lesion in the above image shows characteristic purple, flat, polygonal papules seen in lichen planus.

The lesions of lichen planus can be described as 5Ps — purple, polygonal, pruritic, plane topped

(flat), papules.

Cicatrizing alopecia, flat-topped, purple, polygonal, papules and plaques on the flexural aspect of the wrist, Wickham's striae on the lips, longitudinal ridging, and thinning of nails are features of lichen planus.

Mucous membrane lesions are very common in lichen planus, occurring in almost 30–70 of cases. It is mostly seen on the tongue and buccal mucosa and also on the genitals and anal mucosa.

White streaks forming a lacework in buccal mucosa are a characteristic feature and are known as Wickham’s striae.

Basal epidermal cell degeneration/destruction is characteristically seen in lichen planus.

It occurs because of the basal keratinocytes being destroyed by dermal CD8+ T lymphocytes. Degenerating/apoptotic basal epidermal cells are known as colloid bodies (cytoid/Civatte bodies), which may appear singly or in clumps.

Other histopathological features of lichen planus:

• Hyperkeratosis and hypergranulosis
• Pigment incontinence - melanin gradually moves into the dermis as a result of keratinocyte degeneration
• Dermal melanin is then engulfed by the macrophages forming melanophages

(melanin-containing macrophages).

• The degeneration leads to the formation of spaces in the epidermis known as Max-Joseph spaces.
• The rete ridges are pointed at their lower end giving them a saw-toothed appearance.
• Band-like lymphocytic infiltrate is present at the dermoepidermal junction.
• The image below show the HPE of lichen planus.

Dorsal nail pterygium (image C) is the most specific nail change in lichen planus.

The image below shows thinning of nail plate and longitudinal striations - the most common feature.

The image shows purple, polygonal, flat-topped papules and plaques along with Wickham's striae on the dorsum of the hand, and similar lesions present on the vulva, the age of the patient point towards a diagnosis of lichen planus. The main treatment in the case of persistent lichen planus is steroids.

First-line therapy is always topical steroids.

Second-line treatment is with systemic steroids, retinoids, and PUVA.

Lichen nitidus has a characteristic histopathology of 'claw clutching a ball' appearance as shown in the image.

Lichen nitidus presents with tiny pinhead-sized flesh-colored papules mainly on the dorsum of forearms or penis. Lichen nitidus is considered to be a variant of lichen planus as both are histologically similar in early lesions.

Ball and claw configuration: The ball is comprised of well-circumscribed granulomatous infiltrate of lymphocytes, epithelioid cells and occasional Langhans giant cells that are clutched by surrounding hyperplastic rete ridges, giving the overall "claw clutching ball" appearance.

Lesions are usually asymptomatic and rarely require any treatment.

The image below shows histology of lichen nitidus showing well-defined granuloma enclosed by rete pegs giving the appearance of 'claw clutching a ball'.

Most cases of lichen nitidus occur in children or young adults.

It presents with tiny pinhead-sized flesh-colored papules mainly on the dorsum of the forearms or penis. It is histologically similar to the early lesions of lichen planus. Mucous membrane involvement is quite rare. True Koebner's phenomenon is seen.

Lesions are self-resolving and no treatment is required.

Woronoff's ring is a skin condition characterized by a blanched halo of approximately uniform width surrounding psoriatic lesions after phototherapy or topical treatments.

A major cause of the Woronoff ring is suspected to be due to alterations in prostaglandin metabolism.

Herald patch is seen in pityriasis rosea.

The image shows prominent erythema and scale on the palms of the hands and wrists with marked orangeyellow palmoplantar keratoderma which is a feature of pityriasis rubra pilaris.

Features of pityriasis rubra pilaris:

• Salmon red or orange red-colored dry scaly plaques are seen characteristically, which coalesce together, leaving islands of normal skin, typically known as 'islands of sparing' in between the lesions
• Most common site - trunk
• On the elbow and wrist, nutmeg grater papules are seen due to follicular hyperkeratosis
• Palmoplantar keratoderma - keratoderma on the sole is very thick that it appears as a sandal.
• (keratotic sandal)
• Nails - thickened, discoloured distally, showing splinter hemorrhages
• The image below shows islands of sparing in pityriasis rubra pilaris.

The image below shows keratotic sandal.

This is an image of erythematous follicular hyperkeratosis, parakeratosis, and acanthosis with characteristic islands of sparing as seen in pityriasis rubra pilaris. This is mainly seen over the elbows, knees, wrists, and back of fingers.

Clinical features of pityriasis rubra pilaris:

• Nutmeg grater appearance
• Welldefined salmonred or orange-red dry scaly plaques, which may coalesce and become widespread
• Typically islands of normal skin are present - ‘islands of sparing’
• Starts on the scalp before spreading down over the rest of the body
• Some patients may become erythrodermic
• Pruritus (early stages)

The image below shows a nutmeg grater

Image 1 shows circinate balanitis characterized by small, shallow, painless ulcerative lesions on the glans penis. Image 2 shows keratoderma blenorrhagica characterized by skin lesions seen over the palms and soles which begin as vesicles on erythematous bases and progress to pustular keratotic lesions that coalesce to form plaques. Keratoderma blenorrhagica and circinate

balanitis are both features of Reiter's syndrome. The classical triad of Reiter's syndrome consists of:

• Urethritis
• Acute non-purulent seronegative arthritis
• Conjunctivitis

Note: Keratoderma or keratotic sandals is seen in pityriasis rubra pilaris.

The image shows a collarette scale which is a fine, peripherally attached and centrally detached scale at the edge of an inflammatory lesion. It is seen in pityriasis rosea.Pityriasis rosea is an acute selflimiting disease affecting mainly children and young adults. It is characterized by a distinctive skin eruption and minimal constitutional symptoms. It is associated with human herpesvirus 7 and 6 (HHV-7 amp; HHV-6).

Appearance of scales:

• Herald patch - Large and conspicuous eruptions on the thigh, upper arm, trunk or neck covered by fine scales
• After 5-15 days, it turns into discrete oval lesions, dull pink in colour and covered by fine dry silvery-grey scales.
• It is followed by a marginal collarete of scale with a central clearing. The scales are attached peripherally with the free edges attached internally. It is also called hanging curtain sign
• The long axes of the lesions characteristically follow the lines of cleavage parallel to the ribs
• in a christmas tree pattern on the upper chest and back.

Option A: Annular lesions with central clearing and peripheral scaling, associated with severe itching are characteristic of tinea corporis.

Option D: In icthyosis vulgaris, dry, fine fish-like scales are noted.

Option B: Seborrheic dermatitis shows red, itchy flaky scales over the scalp and other seborrheic areas.

The image below shows a Herald patch.

The given image shows a typical erythematous psoriatic plaque with silvery-white scales. The site of predilection in psoriasis is usually extensor areas.

Option A: Lichen planus presents with plane, polygonal, purple, pruritic, papules (5Ps).

Option C: Pemphigus presents with erosions on the skin and flaccid blisters.

Option D: Pityriasis rubra pilaris presents with red follicular hyperkeratotic papules on the trunk with islands of sparing.

The image shows plaque psoriasis of the dorsum of the hand, and isomorphic or Koebner phenomenon is associated with the condition.

Option B: Meyerson phenomenon refers to the formation of an eczematous ring around a melanocytic nevus.

Option C: Gottron's papules are violaceous, erythematous papules overlying the dorsal interphalangeal or metacarpophalangeal, elbow, or knee joints.

Option D: Nikolsky sign refers to easy peeling of skin on applying tangential pressure over a bony prominence and is classically seen in pemphigus and staphylococcal scalded skin syndrome.