Journal of Medical Cases, ISSN 1923-4155 print, 1923-4163 online, Open Access
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Case Report

Volume 16, Number 2, February 2025, pages 69-76

An Adverse Double-Hit by Pembrolizumab: A Case Report of Bullous Pemphigoid and Pneumonitis

Figures

↓  Figure 1. Tense bulla with clear fluid on the right upper extremity of the patient. Note the erythematous rash with erosions and blistering.
Figure 1.
↓  Figure 2. The chest X-ray showed a nonspecific pattern of bilateral interstitial infiltrates.
Figure 2.
↓  Figure 3. Chest CTPA reveals the presence of honeycombing, traction bronchiectasis, and ground glass opacities suggestive of nonspecific interstitial pneumonitis. CTPA: computed tomography pulmonary angiogram.
Figure 3.
↓  Figure 4. The clinical presentation and the histopathology of bullous pemphigoid.
Figure 4.
↓  Figure 5. The clinical presentation of pneumonitis.
Figure 5.

Tables

↓  Table 1. The Vital Signs and the Laboratory Values of the Initial Diagnostic Workup in the ED
 
Laboratory parameters On admission Reference range
ED: emergency department.
Blood pressure 133/74 mm Hg
Heart rate 107
Respiratory rate 30
Temperature 37.6 °C
Oxygen saturation 75%
Electrocardiogram Normal
High-sensitivity troponin I 150 pg/mL 0 - 34 pg/ml
D-dimers > 20 mg/L 0 - 0.5 mg/L
Lactate dehydrogenase 400 U/L 120 - 230 U/L
C-reactive protein 43.6 mg/dL < 0.5 mg/dL
White blood cells (/µL) 17,960 4,000 - 11,000
Neutrophils 86% 50-70%
Lymphocytes 6% 20-40%
Hemoglobin 8.6 g/dL 13 - 17 g/dL
Platelets (/µL) 449,000 150,000 - 400,000

 

↓  Table 2. Treatment of Bullous Pemphigoid (BP) Secondary to Immunotherapy Depending on the Severity of the Rash
 
Severity of BP secondary to immunotherapy Discontinuation of immunotherapy Treatment
N/A: not available.
Grade 1: < 10% of body surface area (BSA) No Consider oral corticosteroids (0.5 - 1 mg/kg/day) and non-steroidal immunosuppressants
Grade 2: 10-30% of BSA No Treatment as above
Grade 3: > 30% of BSA Yes Add oral or intravenous corticosteroids (1 - 2 mg/kg/day)
Consider non-steroidal immunosuppressants
Grade 4: > 30% of BSA and life-threatening complications, e.g., fluid/electrolyte disorders, intensive care is necessary Yes Add intravenous corticosteroids (1 - 2 mg/kg/day)
Consider non-steroidal immunosuppressants
All grades N/A Topical corticosteroids, topical emollients, oral antihistamines
Tapering of systemic corticosteroids for at least 1 month
Non-steroidal immunosuppressants: dapsone, doxycycline, mycophenolate mofetil, cyclophosphamide, azathioprine, omalizumab, dupilumab, rituximab, intravenous immunoglobulin

 

↓  Table 3. Management of Pneumonitis Secondary to Immunotherapy Depending on the Severity
 
Severity of pneumonitis secondary to immunotherapy Definition Discontinuation of immunotherapy Administration of corticosteroids
P. jirovecii: Pneumocystis jirovecii; N/A: not available.
Grade 1 Subclinical; observation without treatment Temporary No
Grade 2 Mild presentation; outpatient treatment indicated Temporary Prednisone 1 - 2 mg/kg/day with a taper; consider gastrointestinal and P. jirovecii prophylaxis
Grade 3 Severe presentation; inpatient treatment indicated Permanent Prednisone 1 - 2 mg/kg/day with a taper; consider gastrointestinal and P. jirovecii prophylaxis
Grade 4 Life-threatening; mechanical ventilation indicated Permanent Prednisone 1 - 2 mg/kg/day with a taper; consider gastrointestinal and P. jirovecii prophylaxis
Grade 5 Death N/A N/A

 

↓  Table 4. Reported Cases of Bullous Pemphigoid and Pneumonitis in Patients Treated With Pembrolizumab
 
No. Author Sex/age (years)/malignancy Diagnosis; interval between treatment with pembrolizumab and irAE Treatment Outcome
NSCLC: non-small cell lung carcinoma; irAE: immune-related adverse event.
1 Correia et al, 2022 [1] Male/81/bladder cancer Pruritus; 15 weeks Pneumonitis: discontinuation of pembrolizumab Bullous pemphigoid: improvement after 10 days
Pruritus/bullous pemphigoid: topical clobetasol, oral prednisolone, doxycycline, antihistamine
Pneumonitis; 33 weeks
Bullous pemphigoid; 36 weeks
2 Cardona et al, 2021 [2] Male/73/lung adenocarcinoma (NSCLC) Pneumonitis (grade 2) Adrenal insufficiency: corticosteroids Pneumonitis, adrenal insufficiency: resolution
Adrenal insufficiency; 75 weeks (25 cycles) Bullous pemphigoid: lack of response to corticosteroids and infliximab, resolution with cyclophosphamide
Bullous pemphigoid; 2.5 years (35 cycles) Bullous pemphigoid: intravenous methylprednisolone, infliximab, oral cyclophosphamide
3 Alsabbagh et al, 2023 [3] Male/68/bladder cancer Hypertrophic lichenoid dermatitis; 3 months Hypertrophic lichenoid dermatitis: topical mometasone Hypertrophic lichenoid dermatitis: resolution
Bullous pemphigoid; 12 months Bullous pemphigoid: transient discontinuation of pembrolizumab, oral prednisolone, and topical corticosteroids Bullous pemphigoid: resolution within 2 months
Pneumonitis Pneumonitis: permanent discontinuation of pembrolizumab
4 Male/66/lung squamous cell carcinoma (non-small cell lung cancer) Bullous pemphigoid; 16 months (21 cycles) Bullous pemphigoid: topical clobetasol, oral bilastine Bullous pemphigoid: improvement with topical corticosteroids, resolution with systemic corticosteroids within 2 weeks
Pneumonitis (grade 3); 17 months (21 cycles) Pneumonitis: discontinuation of pembrolizumab, intravenous methylprednisolone with proton pump inhibitor Pneumonitis: gradual resolution within 2 weeks