Presenting Complaint:

• Jordan has presented with blistering lesions on his trunk and upper limb.

• Quote:
  “The blistering lesions started 5 days ago on my chest; now they have spread to nearly my whole upper body in 5 days.”

Symptoms (SOCRATES):

• Site: On my trunk and upper limbs
• Onset: 5 days ago
• Character: Fluid-filled blisters which are very fragile and rupture easily. No scars are left. Very painful in the ruptured areas.
• Radiation: N/A
• Associated symptoms: Oral ulcers in my mouth, which have been present for a month. “I thought it was a stress ulcer, so I was keeping an eye on it, when I developed blisters on my body”
• Time: Ongoing for 5 days
• Exacerbating/Alleviating factors: Spontaneously getting worse. No use of topical medications to alleviate the lesions. “I tried steroid cream for my mouth ulcer, but it did not work”
• Severity: Very severe, unable to work or continue with daily activities

Other Negative Findings:

• No nail involvement

Systemic Review:

• Difficulty eating / dysphagia – Yes, mouth ulcers are very sore when eating.
• Weight loss, loss of appetite, night sweats – No
• Fever – No
• Fatigue – Yes, has not slept well for several days due to pain
• Headache or dizziness – No
• Eye involvement – No
• Bone pain – No
• Lymphadenopathy or masses – No
• Cough, dyspnoea, or haemoptysis – No
• Chest pain, palpitations – No
• Change in bowel habit – No
• Urinary symptoms – No

Past Medical History:

• Hypertension
• No history of skin disease
• No history of malignancy
• No previous history of hospitalisation or surgery
• Generally healthy, fully vaccinated

Drug History:

• Ramipril 5 mg once a day, started 3 months ago

Allergies:

• No known drug allergies
• No atopy or allergy history, such as hay fever

Social History:

• Occupation: Farmer
• Smoking: 10 cigarettes a day
• Alcohol: Social drinker
• Functional status: iADLs
• Travel: none recently

Family History:

• No family history of cancer
• No family history of skin disease

Ideas, Concerns, and Expectations:

• Ideas: Thinks this is an infection
• Concerns: Anxious about the possibility of developing sepsis
• Expectations: Expects a clear diagnosis of the lesions and a treatment plan

Observations:

• Respirations: 18/min
• SpO₂: 99% on air
• Blood Pressure: 132/78 mmHg
• Pulse: 82 bpm
• Consciousness: Alert and oriented
• Temperature: 36.8°C

NEWS Total Score: 0

General Inspection:

Appears mildly anxious, though not systemically unwell. Extensive upper limb and trunk skin lesions evident. Jordan is a white British male with pale white skin and light brown hair.

Inspection of the Lesions:

• Distribution: Multiple ruptured and intact blistering lesions of different sizes and ages. Extensive skin lesions with mucosal lesions limited to oral cavity (no anogenital involvement).
• Size: Various sizes ranging from 1 cm to 5 cm
• Shape: Flaccid bullae; erosions present. Nikolsky sign positive
• Colour: Erythematous erosions at the sites of ruptured blisters and clear, straw-coloured fluid-filled blisters
• Margins: None
• Bleeding: No active bleeding
• Surrounding skin appears normal
• Bilateral oral mucosal ulcerations present, with poor dental hygiene
• Nails and hair appearance are normal
• Lymph nodes: No palpable lymph nodes

Images sourced from DermNet in accordance with image licencing policy. https://dermnetnz.org/topics/pemphigus-vulgaris. CC BY-NC-ND 4.0.

Patient Communication Questions:

1. Is this an infection and will I get sepsis?

At the moment, this looks like an autoimmune reaction causing your skin lesions, most likely a condition called pemphigus. Although it is not caused by an infection, the breaks in your skin will make you more vulnerable to infection until they are healed.

2. Why did this happen and what is the cause?

This is an autoimmune reaction in which your immune system attacks key structures in the skin. In pemphigus this is a protein called desmoglein. In your case, a potential trigger may be the Ramipril you recently started, which is a known trigger.

3. What is the next step?

First, we need to stop ramipril, which may be the culprit. We will monitor your blood pressure and consider alternative medications. We will need to take a biopsy from your skin to diagnose you. I will refer you to a dermatologist for the biopsy, further management, and follow-up. In the meantime, we will start steroids to calm down your immune system. We will also send blood tests to check for any infection, and order a chest X-ray to check the lungs. You should see your dentist for oral ulcer management and dental care.

4. What about my blood pressure, the pain, and the lesions?

We will monitor your blood pressure and consider switching your antihypertensive medication. For your mouth ulcers, we’ll provide antiseptic mouthwash and pain relief. For your skin, we’ll ensure proper wound care with low-adhesive dressings, emollients, and compresses. We’ll also make sure you’re getting enough nutrition for proper recovery. Since we are starting steroids, we’ll begin bone protection with vitamin D and calcium.

Examiner Questions:

1. What is your differential diagnosis?

• Pemphigus (drug-induced):
  This is suggested by the presence of flaccid blisters with painful erosions on the skin and mucosa. The lesions are Nikolsky-positive. There is a likely medication-related trigger with the recent introduction of ramipril.
• Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN):
  This is a key differential due to the positive Nikolsky sign. However, patients with SJS/TEN are often systemically unwell.
• Linear IgA Bullous Dermatosis:
  More common in children and associated with drugs (e.g., vancomycin). Considered due to the history of sun exposure, oozing lesions, and size (>7 mm). Has a distinct immunofluorescence staining profile.
• Bullous Pemphigoid:
  An autoimmune disease of the elderly, characterised by tense skin blisters (rather than flaccid) and minimal oral involvement. Often pruritic, with urticarial plaques forming vesicles. Also distinguished histopathologically by direct immunofluorescence findings.
• Epidermolysis Bullosa Acquisita (EBA):
  Characterised by tense blisters and fragile skin. Scarring is common due to antibodies targeting type VII collagen.

2. Which investigations would you request?

• Skin biopsy with Haematoxylin and Eosin (H&E) staining. Skin or mucosal specimens should include intact epidermis immediately adjacent to active blisters or erosions. Biopsies of erosions themselves can result in a false-negative test as there is no epidermis remaining for interpretation.

Histopathology findings suggestive of pemphigus: 

• Changes in epidermal, dermal, and basal cells
• In pemphigus vulgaris (PV), there is intraepidermal blister formation due to acantholysis (loss of keratinocyte adhesion) – while maintaining adhesion to the basement membrane, this gives a tombstone appearance. 
• In pemphigus foliaceus (PF), superficial bullae with a split directly beneath the stratum corneum (subcorneal), while in PV bullae are often suprabasal.
• In paraneoplastic pemphigus (PNP), histopathology findings can mimic pemphigus (i.e., tombstone appearance of the basal cells), erythema multiforme, and lichen planus.

• Direct immunofluorescence (DIF) of biopsy specimens to confirm pemphigus. Skin or mucosal specimens should include intact epidermis immediately adjacent to active blisters or erosions. Direct Immunofluorescence (DIF) of biopsy is the gold standard to confirm pemphigus, which demonstrates intercellular IgG and C3 deposition throughout the epidermis, producing a “chicken wire” or “fishnet” pattern. Seen in all pemphigus subtypes, confirming the autoimmune nature.
• Send serum ELISA to check for anti-desmoglein 1 and 3 antibodies.
• Order blood tests (FBC, CRP, U&Es) to monitor inflammation and infection risk.
• Request chest X-ray or CT thorax to rule out pulmonary involvement (if respiratory symptoms or suspecting paraneoplastic pemphigus).
• Screen for lymphoproliferative disorders if clinical suspicion is raised (e.g., blood film, LDH).

3. What is your treatment plan?

• Initially, stop ramipril, which is a potential trigger for bullous lesions.
• Commence systemic corticosteroids, oral prednisolone, typically 0.5–1 mg/kg/day, depending on severity. If widespread or severe, consider IV methylprednisolone or pulse steroids. Start bone protection (calcium and vitamin D) and PPI with steroid therapy.
• Urgent dermatology referral for diagnostic investigations (biopsy / immunofluorescence / ELISA) and specialist management such as immunosuppressives / Rituximab / IVIG, and follow up. These will cause immunosuppression and appropriate patient counselling is required.
• In confirmed paraneoplastic pemphigus, further management will require oncology input.

Supportive treatment:

• For wound care and infection prevention, apply low-adhesive dressings, emollients, and compresses to protect erosions.
• Monitor for signs of secondary infection in ruptured areas.
• Consider antiseptic washes and topical antibiotics if indicated.
• Provide adequate analgesia for ruptured lesions and painful oral ulcers.
• Use antiseptic or corticosteroid mouthwashes for oral mucosal involvement.
• Dentist referral for oral hygiene and ulcer care.
• Consider dietitian input if oral intake is reduced due to mucosal pain.
• Ask primary care to monitor blood pressure and consider alternative antihypertensive therapy.