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.
However, there are not yet randomized trials assessing which protocol is better in terms of efficacy and safety. On the other hand, high dose regimens should be preferred instead of low-dose regimens, due to longer disease response. 9
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 linked with an underlying rheumatologic condition (n = 17, 51.5%), most commonly Sjögren’s syndrome (44.4%). The classic triad of serum sickness (fever, rash, and arthralgia) was reported in 16 (48.5%) cases. Time from drug exposure to symptom onset was significantly greater with the first doses of RTX compared to the second dose (mean time 10.00 vs. 4.05 d, P = 0.002), and time to resolution was significantly greater for rheumatologic vs. hematological indications (mean time 2.50 vs. 1.00 d, P = 0.035).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.