Pemphigus vulgaris case study
The case
Patient: A 48‑year‑old male, accountant, non‑smoker, no known drug allergies.
Presenting complaint: Painful oral erosions for 3 weeks, now associated with flaccid blisters on the trunk and scalp for 5 days.
History of present illness:
- Three weeks ago he noticed a burning sensation on the buccal mucosa, followed by small erosions that coalesced into larger painful ulcers, making it difficult to eat solid food.
- Five days ago, he observed flaccid, translucent vesicles on his chest and scalp that ruptured within a few hours, leaving raw, tender erosions that bleed on minor trauma.
- He reports mild pruritus preceding the skin lesions but denies any prior similar episodes.
- No fever, weight loss, night sweats, or recent infections.
- No recent medication changes, herbal remedies, or travel.
Past medical history: Hypertension diagnosed 5 years ago, controlled on amlodipine 5 mg daily. No prior dermatologic disease.
Family history: Mother with rheumatoid arthritis; brother healthy.
Social history: Lives with wife and two children; works long hours at a desk; occasional alcohol (1–2 drinks/week).
Review of systems: Negative for joint pain, photosensitivity, gastrointestinal bleeding, or respiratory symptoms.
Examination:
| Parameter | Finding |
|---|---|
| General | Alert, mildly distressed by oral pain |
| Vitals | BP 138/84 mmHg, HR 88 bpm, RR 16 /min, Temp 37.2 °C, SpO₂ 98 % on room air |
| Skin | Multiple flaccid bullae (0.5–2 cm) on erythematous base over the chest, upper back, and scalp; after rupture, shallow erosions with peripheral erythema, positive Nikolsky sign (gentle lateral pressure on adjacent skin produces new erosion). No target lesions, no mucosal involvement elsewhere. |
| Oral cavity | Extensive erosions on buccal mucosa, palate, and lateral tongue; surrounding erythema, no crusting. |
| Lymph nodes | No cervical, axillary or inguinal lymphadenopathy. |
| Other systems | Unremarkable. |
Initial investigations:
| Test | Result |
|---|---|
| CBC | Hb 13.2 g/dL, WBC 9.8 × 10⁹/L (Neut 72 %, Lymph 22 %), Platelets 250 × 10⁹/L |
| Serum electrolytes | Na 138 mmol/L, K 4.2 mmol/L, Cl 102 mmol/L, HCO₃⁻ 24 mmol/L |
| Renal function | BUN 14 mg/dL, Creatinine 0.9 mg/dL |
| Liver function | AST 22 U/L, ALT 24 U/L, ALP 78 U/L, Bilirubin 0.8 mg/dL |
| Fasting glucose | 92 mg/dL |
| Tzanck smear (from ruptured blister) | Acantholytic (Tzanck) cells, no multinucleated giant cells |
| Direct immunofluorescence (DIF) of perilesional skin | Intercellular IgG and C3 deposition in a “fish‑net” pattern |
| ELISA for desmoglein‑3 antibodies | Positive, 115 U/mL (reference < 14 U/mL) |
| ANA, anti‑dsDNA | Negative |
| Chest X‑ray | Normal |
Questions
- What is the most likely diagnosis?
- Which clinical and laboratory findings support this diagnosis, and why do they point toward it?
- List the investigations required to confirm the diagnosis and to assess disease severity.
- Outline the acute‑phase management plan, including first‑line therapy and steroid‑sparing options, with dosing recommendations.
- Discuss potential complications of the disease and of its treatment, and how they can be prevented or monitored.
Answers
1. What is the most likely diagnosis?
Pemphigus vulgaris (PV) – an autoimmune intra‑epidermal blistering disease characterized by IgG auto‑antibodies against desmoglein‑3 (and sometimes desmoglein‑1), leading to loss of keratinocyte adhesion (acantholysis).
Rationale: The combination of painful oral erosions preceding skin involvement, flaccid bullae that rupture easily, a positive Nikolsky sign, and the presence of intercellular IgG on DIF is classic for PV.
2. Which clinical and laboratory findings support this diagnosis, and why do they point toward it?
| Finding | Explanation |
|---|---|
| Painful oral erosions (first symptom) | Desmoglein‑3 is highly expressed in mucosal epithelium; antibodies target this protein early, producing mucosal lesions before cutaneous disease. |
| Flaccid bullae on trunk & scalp | Intra‑epidermal (suprabasal) blisters are thin‑walled and rupture easily, unlike the tense bullae of bullous pemphigoid (subepidermal). |
| Positive Nikolsky sign | Mechanical shear separates weakened keratinocytes, a hallmark of PV and other pemphigus disorders. |
| Tzanck smear showing acantholytic cells | Direct cytologic evidence of loss of intercellular connections; helps differentiate from herpes simplex (multinucleated giant cells). |
| DIF with intercellular IgG & C3 (“fish‑net”) | Pathognomonic for pemphigus; the IgG binds to desmosomes throughout the epidermis. |
| Elevated desmoglein‑3 ELISA | Quantifies disease‑specific auto‑antibodies; high titres correlate with disease activity. |
| Absence of target lesions, negative ANA | Helps exclude other blistering diseases (e.g., erythema multiforme, lupus). |
These findings collectively satisfy the diagnostic criteria set by the International Pemphigus Committee (2020) which require: (i) clinical features of flaccid blisters/erosions, (ii) histopathology showing suprabasal acantholysis, and (iii) immunopathology demonstrating intercellular IgG deposition.
3. List the investigations required to confirm the diagnosis and to assess disease severity.
| Investigation | Purpose | Typical result in PV |
|---|---|---|
| Skin biopsy (H&E) | Histopathology – demonstrates suprabasal cleft with “row of tombstones” of basal keratinocytes. | Suprabasal acantholysis. |
| Direct immunofluorescence (DIF) | Gold‑standard immunopathology. | Intercellular IgG & C3 in fish‑net pattern. |
| Indirect immunofluorescence (IIF) on monkey esophagus | Detect circulating auto‑antibodies; more sensitive for mucosal PV. | Positive IgG binding. |
| ELISA for desmoglein‑1 & desmoglein‑3 | Quantifies specific antibodies; guides prognosis (high Dsg‑3 → mucosal disease). | Elevated Dsg‑3 (often > 100 U/mL). |
| Complete blood count & metabolic panel | Baseline before systemic steroids/immunosuppressants; monitor for drug toxicity. | Usually normal initially. |
| Hepatitis B/C, HIV, TB screening | Required before initiating rituximab or other biologics. | Negative. |
| Pregnancy test (if applicable) | Certain drugs are teratogenic. | Not applicable here. |
| Baseline ophthalmologic exam | Long‑term steroids can cause cataracts/glaucoma. | Normal. |
| Disease severity scoring (e.g., PDAI – Pemphigus Disease Area Index) | Objective measurement for treatment response. | PDAI score ≈ 45 (moderate‑severe). |
4. Outline the acute‑phase management plan, including first‑line therapy and steroid‑sparing options, with dosing recommendations.
a. Immediate measures
- Hospital admission (or day‑care) for close monitoring of fluid loss, nutrition, and infection risk.
- Wound care – non‑adherent dressings (e.g., silicone‑coated), gentle cleansing with normal saline, topical antimicrobial (e.g., mupirocin 2 % ointment) on secondary bacterial colonisation.
- Analgesia – paracetamol 1 g q6h; consider low‑dose opioid (e.g., tramadol 50 mg q6h) if pain uncontrolled.
b. Systemic therapy
| Drug | Dose & Regimen | Rationale | Guideline reference |
|---|---|---|---|
| Prednisone (or prednisolone) | 1 mg/kg/day (≈70 mg/day) orally, divided BID; taper after disease control (usually over 4–6 weeks). | Rapid control of auto‑antibody production; first‑line per BAD 2022 & AAD 2023. | British Association of Dermatologists (BAD) Guideline for Pemphigus, 2022. |
| Azathioprine (steroid‑sparing) | 2 mg/kg/day (≈150 mg/day) orally, start after 1–2 weeks of steroids; check TPMT activity before initiation. | Reduces cumulative steroid dose; effective in 60‑70 % of patients. | BAD 2022; European Dermatology Forum (EDF) 2021. |
| Rituximab (if disease severe or refractory) | 1 g IV on day 0 and day 14 (two‑dose protocol) OR 375 mg/m² weekly × 4 weeks (R‑CHOP protocol). | B‑cell depletion leads to durable remission; now first‑line in many centres per 2023 AAD update. | AAD 2023 Guideline, “Rituximab as first‑line for moderate‑severe PV”. |
| Mycophenolate mofetil (alternative steroid‑sparing) | 1 g BID (2 g/day) orally; adjust for renal function. | Useful when azathioprine contraindicated. | BAD 2022. |
| Intravenous immunoglobulin (IVIG) (adjunct) | 2 g/kg divided over 5 days, repeat monthly if needed. | Consider in refractory cases or when infection risk precludes high‑dose steroids. | AAD 2023. |
c. Adjunctive therapies
- Proton‑pump inhibitor (e.g., omeprazole 20 mg daily) to prevent steroid‑induced gastritis.
- Calcium 1 g + Vitamin D 800 IU daily and bisphosphonate (alendronate 70 mg weekly) for osteoporosis prophylaxis after > 3 months of steroids.
- Vaccinations – influenza annually, pneumococcal (PCV20) before immunosuppression.
d. Tapering strategy
- Once PDAI ≤ 10 and no new lesions for 2 weeks, begin taper of prednisone by 10 % every 1–2 weeks, aiming for ≤ 5 mg/day by 3–4 months.
- Maintain azathioprine (or mycophenolate) for at least 12 months after complete clinical remission before slow discontinuation.
e. Multidisciplinary input
- Dermatology – primary disease control.
- Oral medicine / ENT – management of painful mucosal lesions, nutritional support (soft diet, high‑protein supplements).
- Infectious disease – prophylaxis for opportunistic infections if high‑dose steroids > 20 mg/day for > 4 weeks.
5. Discuss potential complications of the disease and of its treatment, and how they can be prevented or monitored.
| Complication | Disease‑related or Treatment‑related | Prevention / Monitoring |
|---|---|---|
| Secondary bacterial infection (e.g., Staphylococcus aureus cellulitis, sepsis) | Disease (disrupted skin barrier) & steroids (immunosuppression) | Daily wound inspection, topical antiseptics, early systemic antibiotics if signs of infection (fever, ↑WBC). |
| Electrolyte loss & dehydration (due to extensive erosions) | Disease | Monitor fluid balance, replace with isotonic fluids if needed; check electrolytes daily until lesions heal. |
| Oral candidiasis | Steroid use (systemic & topical) | Prophylactic nystatin suspension swish‑spit q6h; treat breakthrough infection with fluconazole 100 mg PO daily for 7 days. |
| Steroid‑induced hyperglycemia | Treatment | Check fasting glucose weekly for first 4 weeks; start metformin if persistent > 126 mg/dL. |
| Hypertension, fluid retention, weight gain | Treatment | Monitor BP weekly; advise low‑salt diet; consider diuretic if edema develops. |
| Osteoporosis & fractures | Long‑term steroids | Baseline DEXA scan; calcium/vit D supplementation; bisphosphonate as above; repeat DEXA at 12 months. |
| Adrenal suppression | High‑dose steroids > 3 months | Perform morning cortisol after taper; educate patient on stress‑dose steroids during illness or surgery. |
| Rituximab‑related infusion reactions & hepatitis B reactivation | Treatment | Premedicate with acetaminophen & antihistamine; screen for HBV (HBsAg, anti‑HBc) and give antiviral prophylaxis if positive. |
| Azathioprine‑related myelosuppression or hepatotoxicity | Treatment | Check CBC & LFTs every 2 weeks for first 2 months, then monthly. TPMT testing before start. |
| Malignancy (non‑melanoma skin cancer, lymphoma) | Chronic immunosuppression | Annual skin examination; counsel on sun protection; consider dermatology follow‑up long‑term. |
Key learning points
- Pemphigus vulgaris is an IgG‑mediated intra‑epidermal blistering disease; desmoglein‑3 antibodies cause mucosal‑predominant lesions, while desmoglein‑1 involvement adds cutaneous disease.
- The classic triad: painful oral erosions, flaccid bullae that rupture easily, and a positive Nikolsky sign.
- Definitive diagnosis requires direct immunofluorescence (intercellular IgG/C3) and ELISA for desmoglein antibodies; Tzanck smear shows acantholytic cells but is not specific.
- First‑line therapy is high‑dose systemic corticosteroids; early introduction of a steroid‑sparing agent (azathioprine, mycophenolate, or rituximab) reduces morbidity.
- Rituximab is now recommended as first‑line for moderate‑to‑severe PV in the 2023 AAD guideline, offering higher remission rates and lower cumulative steroid exposure.
- Monitor for infection, electrolyte disturbances, and steroid‑related adverse effects (hyperglycemia, osteoporosis, adrenal suppression).
- Use disease activity scores (PDAI) to guide treatment intensity and tapering decisions.
- Multidisciplinary care (dermatology, oral medicine, nutrition, infectious disease) improves outcomes and reduces complications.
Practice MCQs
1. Which of the following immunopathologic patterns is most characteristic of pemphigus vulgaris?
A. Linear IgG deposition along the basement membrane zone
B. Granular IgA deposition at the dermal papillae
C. Intercellular IgG and C3 in a “fish‑net” pattern within the epidermis
D. Subepidermal deposition of IgG and C3
Answer: C — Pemphigus vulgaris shows intercellular IgG/C3 binding to desmosomes, giving a fish‑net appearance on direct immunofluorescence.
2. A 45‑year‑old woman with newly diagnosed pemphigus vulgaris is started on prednisone 80 mg daily. Which of the following is the most appropriate prophylactic measure to reduce the risk of steroid‑induced osteoporosis?
A. Calcium 500 mg twice daily only
B. Vitamin D 400 IU daily only
C. Calcium 1 g + Vitamin D 800 IU daily plus alendronate 70 mg
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