Discussion
Rituximab is a novel therapeutic agent for severe and recalcitrant pemphigus vulgaris (PV). 19 In patients with PV, human antichimeric antibodies (e.g., RTX) are known to cause treatment failure and adverse effects especially with intravenous administration20.
Rituximab-induced serum sickness (RISS) has been reported earlier in various autoimmune disorders including rheumatoid arthritis, Sjogren’s syndrome, and hematological malignancies 21. Typically, it has been explained by the presence of the murine component in RTX and B-cell lysis by forming complexes with antibodies due to the delivery of intracellular antigens to the serum which then precipitates systematically in the synovial membranes of joints 22, 23.
A 2015 literature review identified 33 reported cases associated with RTX where most of the reported cases were related to an underlying rheumatologic condition (such as Sjögren’s syndrome). The classic triad (fever, rash, and arthralgia) of serum sickness was reported less than half of cases. The mean time from exposure to symptom onset with the RTX first dose was almost double compared to the second dose.24
A recent study has described the epidemiological and clinical characteristics of 37 cases of RISS reported in France. Serum sickness occurred mainly 12 days after the first injection (54%). The most frequent manifestations were rheumatologic symptoms (92%), fever (87%), and skin lesions (78%). The incidence was significantly higher when RTX was used for autoimmune diseases than for hematological malignancies. 25
The role of RTX in severe refractory PV has been studied in the past few years. Some of the documented adverse effects include severe infections such as pneumonia, progressive multifocal leukoencephalopathy, anaphylaxis, Stevens-Johnson syndrome. 19
In our case, the treating physician did not recommend resuming RTX to prevent any further severe reaction. Mainly, the diagnosis of serum sickness depends on clinical features. Other causes such as malignancy and any infection that can trigger serum sickness should be ruled out. In this case, investigations such as blood investigations (e.g., CBC, complement C3, C4, blood culture. etc.), ultrasonography abdomen, and urine analysis helped in ruling out malignancy and infectious potential causes. In our patient, clinical presentation, medication history, and quick response to treatment helped in making the diagnosis of RISS. Overall, all the clinical features, laboratory findings, quick response to corticosteroids were suggestive of serum sickness due to RTX (which was started two weeks ago) after excluding other possible causes.