Paraneoplastic pemphigus: an association with fludarabine?

Abstract

Paraneoplastic pemphigus is a relatively recently described immunobullous disease with characteristic features. We report three cases of paraneoplastic pemphigus in adult men with chronic lymphocytic leukaemia arising within a week of completion of treatment with fludarabine. In all cases, withdrawal of fludarabine and treatment of the blistering was associated with marked cutaneous improvement. Fludarabine, a synthetic nucleoside analogue, which has only been available in Britain since 1994, is known to be associated with autoimmune phenomena and may have been involved in the development of paraneoplastic pemphigus in these cases.

Chemotherapeutic agents and the skin: An update

“…[196][197][198][199] A blistering disorder resembling erythema multiforme and toxic epidermal necrolysis that was subsequently recognized as paraneoplastic pemphigus (PNP) has also been reported in association with fludarabine. 197,[200][201][202][203] Three patients with longstanding CLL developed PNP within 1 week of completion of treatment of fludarabine. 202 While hematologic malignancy itself, specifically nonHodgkin's lymphoma and CLL, is associated with PNP, the above cases were thought to be linked to the drug, not the disease, because both the skin and mucous membrane involvement improved markedly upon withdrawal of fludarabine and delivery of immunosuppressive therapy in all three patients.…”

Severe breathlessness, mouth ulcers and skin blistering in a female

“…Fludarabine, another antimetabolite, has been implicated in a few patients [12], but PNP with constrictive bronchiolitis can occur in the absence of any drug ingestion in at least a third of patients. Current opinion is that drugs do not play a major role in the aetiology of PNP [13].…”

Chronic lymphocytic leukemia and autoimmunity: a systematic review

“…Whilst the epidemiological evidence discussed above does not suggest an increased risk of AID in CLL, or CLL in AID except immune cytopenia, there are cases in which the CLL clone has been demonstrated to produce a clinically important autoantibody. 97,98,[114][115][116][117][118] There are other cases in which, though CLL and an AID coexist in a patient, there is no evidence of a causal link (Table 4). In other situations, CLL associated with a monoclonal immunoglobulin or light chain causes organ damage, but by a mechanism which does not involve autoimmunity.…”

“…122 This theory is supported by the more recent recognition of PNP in association with treatment with fludarabine. 114 However, PNP does arise in untreated CLL, and has been successfully treated with fludarabinecontaining regimens. 124 It has also been noted that dysregulated cytokine production, particularly IL-6, may be the mechanism by which tumors, including CLL, cause PNP.…”