"Immunobullous Disorders" — Practice

Question 1

Tense blisters that remain intact for days with a negative Nikolsky sign in an 80-year-old indicate

Accepted Answer

A

Question 2

Granular IgA deposits in the dermal papillae on direct immunofluorescence indicate

Accepted Answer

C

Question 3

A 48-year-old has six weeks of painful oral erosions and now flaccid trunk blisters that rupture leaving raw areas. Firm lateral pressure on normal-looking skin shears the epidermis. Diagnosis and confirmatory tests?

Accepted Answer

Pemphigus vulgaris. Painful oral erosions preceding skin disease, flaccid blisters and a positive Nikolsky sign all indicate an intraepidermal split with acantholysis extending into clinically normal skin.

Three tests answer different questions. Histopathology of an intact early blister shows a suprabasal split with a tombstone row of retained basal cells. Direct immunofluorescence on perilesional skin, not on the blister, shows intercellular IgG and C3 in a fishnet pattern. Serum ELISA detects anti-desmoglein 3 with or without anti-desmoglein 1, and the titre can subsequently be used to monitor disease activity.

Question 4

A 78-year-old diabetic on vildagliptin has three months of intense itch with urticarial plaques and now tense limb blisters lasting days. Nikolsky is negative. Diagnosis and the specific action required?

Accepted Answer

Bullous pemphigoid. Tense blisters with a negative Nikolsky sign indicate a subepidermal split, and the long prodrome of itch and urticarial plaques before any blister is characteristic and frequently misdiagnosed as eczema.

The specific action is to review the vildagliptin. Dipeptidyl peptidase-4 inhibitors carry the highest drug-associated risk of bullous pemphigoid of any class, with vildagliptin most strongly implicated, and this is of particular importance in India where gliptins are heavily prescribed. Withdrawal with substitution of an alternative hypoglycaemic can lead to resolution and should be arranged alongside potent topical or systemic corticosteroid.

Question 5

A 30-year-old has intensely itchy grouped vesicles on elbows, knees and buttocks, mostly excoriated. Give the diagnosis, the confirmatory finding and the two components of treatment.

Accepted Answer

Dermatitis herpetiformis, the cutaneous expression of gluten sensitivity. The extensor and buttock distribution with severe itch is characteristic, and intact vesicles are often absent because they are scratched away before presentation.

Direct immunofluorescence on perilesional skin shows granular IgA in the dermal papillae, which distinguishes it from linear IgA disease.

Treatment has two separate components that are often conflated. Dapsone controls symptoms dramatically within days but does nothing for the enteropathy. A strict gluten-free diet treats the underlying coeliac disease, allows dapsone to be withdrawn eventually, and addresses the long-term risk of small bowel lymphoma.

Question 6

Explain why pemphigus foliaceus never involves the mouth while pemphigus vulgaris almost always starts there.

Accepted Answer

Desmoglein compensation. Desmoglein 3 is expressed throughout mucosal epithelium but only in the deeper epidermis, while desmoglein 1 is expressed throughout the epidermis, most strongly superficially, and only weakly in mucosa.

Pemphigus foliaceus antibodies target desmoglein 1 alone. In skin, the superficial epidermis depends on desmoglein 1 with little desmoglein 3 to compensate, so it splits subcorneally. In mucosa, abundant desmoglein 3 compensates fully for the small amount of desmoglein 1 present, so mucosa remains intact.

Pemphigus vulgaris antibodies target desmoglein 3. In mucosa there is too little desmoglein 1 to compensate, so blistering occurs. In skin, desmoglein 1 compensates superficially, which is why mucosal-dominant disease can exist with entirely normal skin until anti-desmoglein 1 antibodies also develop and the disease becomes mucocutaneous.

Question 7

A patient has a positive Nikolsky sign, extensive mucosal ulceration and skin detachment, becoming unwell over four days after starting a new drug. Why is this probably not pemphigus, and how does management differ?

Accepted Answer

Because the tempo and the trigger are wrong. Pemphigus develops over weeks to months, characteristically beginning with oral erosions that persist and only later producing skin blisters. Onset over four days following a new drug points strongly to toxic epidermal necrolysis.

The Nikolsky sign is positive in both, which is exactly why they are confused, but the mechanisms differ. In pemphigus the epidermis splits internally through autoantibody-mediated acantholysis. In toxic epidermal necrolysis the full thickness of the epidermis undergoes keratinocyte necrosis and detaches at the dermo-epidermal junction. Histology separates them decisively.

Management is opposite. Toxic epidermal necrolysis requires immediate withdrawal of the culprit drug and supportive care in a burns or high-dependency setting with attention to fluid balance, temperature, infection and the eyes, rather than the immunosuppression that pemphigus demands.

Question 8

A newly diagnosed pemphigus vulgaris patient is started on high-dose prednisolone alone with a plan for prolonged tapering. Critique this and state what current evidence supports.

Accepted Answer

This reflects the older standard and is no longer the preferred first-line approach. Prolonged high-dose corticosteroid carries a substantial cumulative burden of diabetes, osteoporosis, myopathy, infection and adrenal suppression, and relapse on tapering is common.

The Ritux 3 trial showed rituximab combined with short-term prednisolone to be superior to prednisolone alone, and long-term follow-up reported sustained corticosteroid-free remission in a substantial proportion of patients treated with rituximab first-line. Rituximab has therefore moved to first-line therapy in pemphigus vulgaris.

The mechanism explains the result. Pemphigus is a B-cell-driven autoantibody disease, so depleting CD20-positive B cells removes the source of the pathogenic antibody rather than merely suppressing the downstream inflammation, which is why remission can outlast the drug. Before starting, screening for latent tuberculosis, hepatitis B and, in Indian practice, strongyloidiasis is appropriate, alongside bone protection and glycaemic monitoring for the steroid component.

Question 9

Two patients both show linear IgG at the basement membrane zone. Salt-split skin localises the antibody to the roof in one and to the floor in the other. What does each indicate and why does it matter?

Accepted Answer

Incubating skin in hypertonic sodium chloride splits it artificially through the lamina lucida, so antigens lying above that plane travel with the epidermal roof and antigens lying below stay with the dermal floor.

Antibody on the roof indicates BP180 or BP230, both hemidesmosomal and situated above the lamina lucida, so the diagnosis is bullous pemphigoid or one of its variants. Antibody on the floor indicates type VII collagen, the anchoring fibril protein lying below the lamina densa, so the diagnosis is epidermolysis bullosa acquisita.

It matters because routine direct immunofluorescence cannot separate them, yet they behave and respond very differently. Bullous pemphigoid usually responds well to corticosteroid, including potent topical treatment in localised disease, and is often self-limiting over years. Epidermolysis bullosa acquisita is characteristically treatment-resistant, affects trauma-prone sites, and heals with scarring and milia, so recognising it prevents repeated escalation of a therapy that was never going to work.

Practice — "Immunobullous Disorders"

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