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Rituxan is not associated with Stevens Johnson Syndrome.

After reading a case report published in your journal [1], I am concerned about the presumptive diagnosis of Stevens–Johnson Syndrome (SJS) in the setting of rituximab. The case report documents a relapsing and remitting course of severe mucositis and skin lesions over several months. This patient was being treated for follicular non-Hodgkin’s lymphoma with a regimen that included rituximab. There are several items of concern with respect to this case. SJS, or the more severe form toxic epidermal necrolysis (TEN), is ‘not’ a chronic condition [2]. It is most often drug induced and is characterized by the acute onset of oral erosions and skin necrosis. It is rapidly progressing resulting in complete resolution or death [2] over days to weeks, not months as the case report asserts. The clinical description, pathology, and clinical course in the case report are consistent with paraneoplastic pemphigus (PNP). PNP is a blistering erosive mucocutaneous disease associated with lymphocytic malignancy [3]. In addition to mucositis, it is frequently associated with cutaneous inflammatory lesions mimicking graft-versus-host disease, lichen planus, or erythema multiforme [3]. The diagnosis of PNP or SJS is not exclusively a clinical diagnosis, but should include pathological exam and, in the case of PNP, direct immune fluorescence (DIF). The pathological description in the case report is one of eosinophils and lymphocytic infiltrate in the dermis with epidermal spongiosis and loss of the epidermis. This description is nonspecific and could include any of the items in the above differential [3]. The key to the diagnosis of PNP is DIF, which was not carried out in the published case report. In contrast, SJS and TEN are characterized by full-thickness necrosis of the epidermis and a lack of inflammation, or pauci-inflammatory infiltrate in the dermis [2]. The case report demonstrated opposite findings and therefore did not support a diagnosis of SJS/TEN. Given the lack of pathological correlation with SJS, this calls into question the diagnosis of SJS. It is important to recognize the difference between an acute, life-threatening drug-induced eruption (SJS/TEN) and a symptom of the patient’s underlying medical condition (PNP). In SJS/TEN the course of action is to immediately stop the offending medication [2]. In contrast, treatment of PNP is based on treating the underlying malignancy, which may include continuing rituximab [3]. Our concern with this published case report is that the diagnosis of SJS may be erroneously associated with rituximab in the literature. It is our belief that rituximab is actually associated with PNP due to the underlying diagnosis of lymphoma. PNP can be confused with SJS/TEN clinically, in the absence of appropriate diagnostic measures. We worry that in patients who develop PNP while being treated with rituximab, treatment may be stopped due to suspicion of SJS/TEN. Instead of continuing the rituximab and eradicating the lymphoma and consequently PNP, rituximab may be prematurely discontinued leading to progression of the eruption and worsening condition of the patient. Instead of treating the lymphoma, the patient may eventually die because of the disease. We advocate that in any patient with an SJS/TEN or PNP-like eruption on rituximab, a skin biopsy including DIF must be carried out to distinguish between the two. Only then can the patient be appropriately treated.