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Multiple diagnostic imaging modalities were done, including computed tomography (CT) scans of the chest, neck, abdomen, and pelvis. A positron emission tomography (PET) scan of the brain was also done. Abnormal results are shown in [Table 2].

Skin excisional biopsy from the lesions was done. Results revealed the presence of perivascular subcutaneous inflammatory cell infiltrates, with marked RBCs extravasation suggestive of vasculitis. No evidence of malignancy.

Table: 2. Imaging modalities that were done for the patient with abnormal findings.

Based on the patient’s medical history, clinical examination, and investigations including histopathologic findings, the diagnosis was Rituximab-induced leukocytoclastic vasculitis. Rituximab treatment was stopped, and the patient started taking steroid therapy. In about two months of rituximab discontinuation, the skin lesions disappeared.

Discussion

Rituximab is an anti-CD20 B-cell chimeric monoclonal antibody medication that is commonly used to treat various forms of cancer, including B-cell chronic lymphoid leukemia and follicular non-Hodgkin's lymphoma. However, like all medications, rituximab can also have unintended side effects. One such side effect is vasculitis, which is a rare but recognized complication of rituximab therapy [5]. According to the available literature, our case appears to be the first in the Middle East region and one of the few worldwide cases of biopsy-confirmed rituximab-induced vasculitis.

Here, we present three additional reported unique cases. The first case was a 44-year-old Japanese man who developed vasculitis two days after the first infusion of rituximab, manifesting as a symmetrical, erythematous annular rash on both lower legs [6]. The second case was a 67-year-old American woman who developed hemorrhagic bullae on her upper arms, palms, trunk, thighs and legs after the third dose of rituximab [6]. The third case was a 38-year-old Korean man with rheumatoid arthritis who developed symmetrical, erythematous patches that later became purpuric lesions one day after receiving the first infusion of rituximab [4].

The exact pathomechanism of rituximab-induced vasculitis is still under debate, but the most accepted explanations involve a rituximab-anti rituximab antibody complex reaction and cytokine release syndrome. The latter is thought to be responsible for the systemic side effects through the release of a massive amount of TNF-α and IL-6, which can change the vessel walls and activate a cascade of reactions, resulting in the formation of true vasculitis [7].

It is important to note that before confirming the diagnosis of rituximab-induced vasculitis, other etiologies must be ruled out. This includes a detailed history taking, physical examination, and laboratory tests to exclude infections, autoimmune diseases, and the usage of other associated drugs. In the cases presented in this report, the patients had no signs of infection, autoimmune diseases, internal organ disorders, or positive autoantibody studies, thus excluding ANCA-associated vasculitis. Furthermore, the patients did not develop symptoms such as myalgia, arthralgia, flushing, or headache within 24 hours following the first infusion, ruling out an acute infusion reaction [8,9].

Our case report highlights that while rituximab is a widely used treatment option for patients with systemic vasculitis symptoms, it is also a rare but real cause of vasculitis in skin-limited forms. It is important for healthcare providers to be aware of this potential complication and to properly evaluate patients for vasculitis before and during rituximab therapy.

Conclusion

In conclusion, vasculitides are a group of autoimmune conditions that affect blood vessels, and one subtype is cutaneous small-vessel vasculitis. This case report highlights a rare complication of rituximab, which is cutaneous vasculitis. The patient in this case experienced self-limited symptoms that resolved after a few months, but the long-term outcomes and underlying mechanisms of rituximab-induced vasculitis are not well understood. Further research is necessary to gain a better understanding of this side effect and identify any specific risk factors.