Acute generalized exanthematous pustulosis induced by mycophenolate mofetil: a case complicated with pemphigus foliaceus
Drug-induced skin reactions are a rare but critical concern for people with autoimmune diseases—especially when treatments meant to control one condition trigger unexpected complications. A 2020 case from Peking University People’s Hospital highlights this challenge, linking a common immunosuppressant to a severe skin reaction in a patient already battling another blistering disease.
Xi Chen, Yuan-Meng Yang, Bo Li, Xiang-Qian Li, Cheng Zhou, Jiang Jin, Lin Cai, Jian-Zhong Zhang, and Zhang-Lei Mu from the Department of Dermatology at Peking University People’s Hospital in Beijing reported the case in the Chinese Medical Journal. Their work sheds light on how even well-tolerated drugs can interact with existing autoimmune conditions to cause rare, overlapping symptoms.
Background: AGEP and Pemphigus Foliaceus
Acute generalized exanthematous pustulosis (AGEP) is a rare, drug-driven skin reaction. It typically starts suddenly with widespread, non-follicular sterile pustules (pus-filled bumps) on red skin, often paired with fever and elevated neutrophil (white blood cell) counts. Most cases have a good prognosis with prompt treatment. Pemphigus foliaceus (PF) is an autoimmune blistering disease where the immune system attacks desmoglein 1 (Dsg1), a protein that holds skin cells together. PF causes small blisters that rupture quickly, leaving crusts and erosions.
The Case: A Sudden Reaction to Mycophenolate Mofetil
The patient was a 46-year-old woman with PF, diagnosed three weeks earlier via skin biopsy. She’d been treated with prednisone—gradually increased from 60 mg to 120 mg daily over 20 days—and was improving when mycophenolate mofetil (500 mg twice daily) was added to better control her PF. Mycophenolate mofetil is a first-line immunosuppressant for autoimmune diseases because it reversibly blocks inosine monophosphate dehydrogenase, reducing immune cell activity.
Two days after starting mycophenolate mofetil, the patient developed pustules on her wrist folds. The bumps spread to her elbows and knees, merging into “lakes of pus.” She had mild itching and a positive Nikolsky sign (skin peeling when gently rubbed)—a hallmark of blistering diseases like PF and AGEP.
Diagnosis: Separating AGEP from Other Conditions
Lab tests showed normal blood counts, but a skin biopsy revealed key clues: subcorneal blisters (blisters just under the skin’s surface) filled with neutrophils and acantholytic cells (skin cells that have separated from each other). Direct immunofluorescence for complement C3 (a protein involved in immune reactions) was positive—consistent with both PF and AGEP.
To confirm AGEP, the team used the EuroSCAR AGEP validation score, a tool from the European Study of Severe Cutaneous Adverse Reactions. The patient scored at least 8 (out of a possible 12), meeting criteria for a definite AGEP diagnosis. They ruled out other conditions:
- Subcorneal pustular dermatosis: Excluded by negative IgA and anti-Dsg1 antibodies.
- Pustular psoriasis: Excluded by the absence of parakeratosis (abnormal skin cell maturation).
Treatment and Recovery
Mycophenolate mofetil was stopped immediately. The patient’s prednisone dose (120 mg daily) remained unchanged. On day four, she developed a low-grade fever (38.2°C), which resolved with acetaminophen. The pustules cleared completely within a week.
Why This Case Matters
Drug eruptions like AGEP are rare with mycophenolate mofetil—most reactions to the drug are mild. This case is unique because:
- Overlap with PF: The patient’s pre-existing PF (and related immune dysfunction) may have made her more susceptible to AGEP.
- High-dose prednisone: The steroid likely limited the rash’s spread, delayed fever, and kept neutrophil counts normal—atypical for classic AGEP.
- Histological features: The presence of acantholytic cells (from PF) in AGEP pustules explained the positive Nikolsky sign—a rare combination.
Key Takeaways
This case reminds clinicians to watch for rare drug reactions even in patients on strong immunosuppressants. Mycophenolate mofetil is generally safe, but patients with autoimmune diseases may have altered immune responses that increase their risk of adverse effects. For patients, it underscores the importance of reporting new skin changes immediately—even if a medication has been “safe” before.
The original study was published in the Chinese Medical Journal (2020;133(5):629–630) by the Chinese Medical Association. For more details, access the full paper via: doi.org/10.1097/CM9.0000000000000671
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