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.