Is This Blistering Rash Related to His Diabetes?

Paraneoplastic Pemphigus Due  to Thymoma

A 49-year-old man with a history of diabetes mellitus, tuberculosis, herpes simplex keratitis, and methamphetamine abuse presented from a dermatology clinic with a 2-month history of a progressively worsening blistering rash that had begun on his fingers and hands and had spread to his torso, extremities, face, oral mucosa, and groin (Figures 1 and 2). A skin biopsy was performed, and he was begun on corticosteroids for what was believed to be pemphigus vulgaris. He was admitted to the hospital for concurrent management of his corticosteroid-induced hyperglycemia and for wound care.

Diagnostic tests. Biopsy results revealed intracellular epithelial deposition of immunoglobulin G and C3 consistent with pemphigus. Although paraneoplastic pemphigus antibody serologies were obtained in an attempt to rule out paraneoplastic pemphigus, the results came back negative. However, a chest radiograph obtained to rule out recurrence of tuberculosis revealed a retrosternal clear space that later was found to be an anterior mediastinal mass on computed tomography (CT) of the chest (Figure 3). CT-guided biopsy of the mass revealed spindle cell thymoma.

Outcome of the case. During his hospital stay, the skin lesions markedly improved with the addition of mycophenolate mofetil and clobetasol to his corticosteroid regimen. He was discharged with follow-up for surgical resection of the thymoma, which later was completed with no complications. At 16 months after surgical resection, the patient continued to report no further skin lesions.

Discussion. Pemphigus is a dermatologic disorder characterized by acantholysis (loss of intra-keratinocyte adhesion), which leads to intraepithelial blisters in the skin and mucous membranes.¹ Pemphigus usually is idiopathic and can recur frequently with no apparent cause. In rare circumstances, it can be paraneoplastic in origin.

Pemphigus is an organ-specific human autoimmune disease that is associated with various tumors, autoimmune disorders, and some viral infections. The types of pemphigus are characterized by clinical features and the identification of various autoantibodies.¹ These autoantibodies can be used to differentiate between paraneoplastic pemphigus and pemphigus vulgaris.

Paraneoplastic pemphigus is characterized by antibodies against desmoplakins or desmosomal antigens in the setting of an identified neoplastic disorder. More than half of these neoplastic disorders are lymphoreticular in origin (eg, thymoma, lymphoma, leukemia), with most remaining cases caused by Castleman disease, Kaposi sarcoma, and other sarcomas.²

The pathophysiology of paraneoplastic pemphigus occurring with thymoma is not well understood, but it is believed that damage induced by tumor growth within the thymus diminishes its ability to maintain self-tolerance and allows for development of autoimmune diseases such as pemphigus.³ This hypothesis is supported by reports of cases in which resection of a patient’s thymoma led to full regression of bullous dermatoses, with no further incidence of pemphigus reported.³

In the setting of pemphigus, serologic testing alone may not be adequate to rule out an underlying malignancy as the etiology of bullous dermatoses, and further investigation looking for the tumors that are commonly associated with pemphigus is warranted.² Our case illustrates that despite the use of serologic markers, further workup should be considered in order to rule out rare etiologies of pemphigus, such as neoplastic processes.

References:

1. Kershenovich R, Hodak E, Mimouni D. Diagnosis and classification of pemphigus and bullous pemphigoid. Autoimmun Rev. 2014;13(4-5):477-481.
2. Kaplan I, Hodak E, Ackerman L, Mimouni D, Anhalt GJ, Calderon S. Neoplasms associated with paraneoplastic pemphigus: a review with emphasis on non-hematologic malignancy and oral mucosal manifestations. Oral Oncol. 2004;40(6):553-562.
3. Barbetakis N, Samanidis G, Paliouras D, et al. Paraneoplastic pemphigus regression after a thymoma resection. World J Surg Oncol. 2008;6:83.