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Letters to the Editor

Rituximab-Induced Serum Sickness–Like Reaction

A Histopathologic Viewpoint

Succaria, Farah MD; Sahni, Debjani MD; Wolpowitz, Deon MD, PhD

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The American Journal of Dermatopathology: April 2016 - Volume 38 - Issue 4 - p 321-322
doi: 10.1097/DAD.0000000000000356
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To the Editor:

Serum sickness was first described by Von Pirquet and Schick1 in 1905 and is characterized by fever, an urticarial or morbilliform rash demonstrating leukocytoclastic vasculitis, arthralgia/arthritis, gastrointestinal disturbances, lymphadenopathy, and proteinuria. However, serum sickness–like reaction (SSLR) is used to describe a drug reaction also consisting of an urticarial or morbilliform rash, fever, and arthralgias but does not show evidence of cutaneous or systemic vasculitis.2 Numerous nonbiologic medications have been implicated as the cause of SSLR including antibiotics (such as amoxicillin, cefaclor, cephalexin, and trimethoprim-sulfamethoxazole).3 Biologic immune modulators (such as infliximab,4 omalizumab,5 and rituximab6) have also been associated with SSLR. However, the histologic features of SSLR caused by biologic agents have not been reported to date.

We describe a 33-year-old woman on rituximab for thrombotic thrombocytopenic purpura and who presented with an urticarial rash with associated fever and arthralgia that developed 1 week after treatment (Fig. 1). The rash started on an upper extremity and spread asymmetrically to her trunk and lower extremities. Histologic analysis revealed papillary dermal edema, ectatic blood vessels, and a sparse, superficial-to-mid perivascular lymphocytic infiltrate with neutrophils, rare eosinophils, and neutrophils in blood vessel walls. The specimen lacked changes of leukocytoclastic vasculitis and lacked characteristic mild basal layer vacuolization with rare Civatte bodies seen in exanthematous (morbilliform) drug eruptions (Fig. 2). Histopathologic features of SSLR from this medication have not been reported to date. However, the clinicopathologic correlation of SSLR is supported by the similarity of the biopsy findings in this case to those of the 4 reported cases of SSLR caused by nonbiologic medications (Table 1).

Serum sickness–like reaction. Multiple blanching wheals with associated, peripheral red flare (inset) with some admixed erythematous papules and annular plaques.
Serum sickness–like reaction. Punch biopsy reveals papillary dermal edema, ectatic blood vessels, and a sparse, superficial perivascular lymphocytic infiltrate with neutrophils, rare eosinophils, and neutrophils in blood vessel walls. Changes of leukocytoclastic vasculitis were not present. Black arrow highlights the area shown at higher power (×400 in inset) (hematoxylin–eosin stain, original magnification ×200).
Clinical and Histopathologic Features of Reported Cases of Serum Sickness–Like Reaction

In conclusion, SSLR is often diagnosed based on clinical grounds, and generally a biopsy is not warranted to make the diagnosis. However, in cases when a biopsy is performed, knowledge of the spectrum of histologic changes is crucial to reach the correct clinicopathologic correlation. Our case extends the urticarial/dermal hypersensitivity–like changes reported in SSLR from nonbiologic medications to a biologic agent as well.


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