Kaposi's sarcoma in a patient with pemphigus vulgaris mimicking exacerbation of pemphigus

Abstract Background Kaposi's sarcoma (KS) is a rare multifocal angiogenic tumor often seen in immunocompromised setting such as acquired immunodeficiency syndrome (AIDS) or organ transplantation recipients. Pemphigus vulgaris (PV) is a rare blistering disorder with mucocutaneous involvement for which immunosuppressive therapy has long been the core of treatment. Iatrogenic form of KS has been reported infrequently in pemphigus patients as a result of long‐term immunosuppressive therapy. Case We describe a 39‐year‐old male patient with confirmed diagnosis of PV who developed KS after receiving immunosuppressive agents for his pemphigus. KS was initially localized to the oral cavity with features mimicking exacerbation of his pemphigus. Conclusion This interesting case of KS suggests that dermatologists visiting patients with pemphigus with discomfort in the oral cavity should have a high degree of awareness and consider other differential diagnoses along with merely an exacerbation of PV.


| INTRODUCTION
Pemphigus vulgaris (PV) is a rare blistering disorder with mucocutaneous involvement characterized by producing autoantibodies against desmogleins (Dsg) which play an important role in maintenance of cell-to-cell adhesion. 1 Immunosuppressive therapy has long been the core of treatment for pemphigus, [2][3][4][5] though might lead to some serious adverse effects such as susceptibility to neoplastic events. 6,7 Kaposi's sarcoma (KS) is a rare multifocal angiogenic tumor usually presents with violaceous patches and papules of the skin or mucosal area and often seen in immunocompromised setting such as acquired immunodeficiency syndrome (AIDS) or organ transplantation recipients. 8 Iatrogenic form of KS has been reported infrequently in patients with pemphigus due to long-term immunosuppressive therapy. 9 Here, we present a case of KS, presented in an Iranian known case of PV with features might have led to misdiagnosis of exacerbation of his pemphigus. He was firstly presented with painful oral ulcers and widespread cutaneous erosions mainly over truncal area for 3 months.

| CASE REPORT
Histopathologic and DIF examinations stablished the diagnosis of PV. His disease had initially been controlled with 60 mg/day prednisolone which tapered to 30 mg/day during 1 month and rituximab (one cycle consisting of one infusion of 500 mg every week for 4 weeks) was added to his therapeutic regimen leading to a considerable clinical improvement. Hence, prednisolone was rapidly tapered to 10 mg/day in 3 months because of his cushingoid appearance and also achieving partial clinical remission. The Pemphigus Disease Area Index (PDAI) score of cutaneous and mucosal lesions from 11 and 10 at the baseline, declined to 0 and 3 at the fifth month of treatment, respectively.
The patient had also taken Isoniazide (INH) and vitamin B6 as tuberculosis prophylaxis due to positive skin tuberculin test (induration: 13 mm). Patient was otherwise healthy.
By the time, the prednisolone dosage was lowered to 7.5 mg/day and cutaneous PDAI score was 0, but he was still complaining of a persistent odynophagia and dysphonia.
On physical examination, the patient had generally good health and no remarkable finding was noted except for mild sore throat and an erythematous nodule with erosive surface at the end of lingual area ( Figure 1). Although it initially was assumed to be a vegetative lesion of his pemphigus, but the unusual morphological appearance of lesion including its mild violaceous hue, led us to consider the possibility of a secondary pathologic process in this area.
MRI of cervical soft tissue revealed an isosignal 23 Â 73 mm mass at oropharyngeal region on epiglottis which was enhanced after contrast injection. Pressure effect on airway was also noted.

| DISCUSSION
KS is an angioproliferative neoplasm of low-grade malignant potential. 10 Its exact etiopathogenesis is not completely understood, but impaired immunity and HHV-8 virus infection along with angiogenic milieu due to inflammatory cytokines could lead to the disease development. 11,12 It is hypothesized that altered immunity weakens the immunological surveillance and leads to reactivation of a latent HHV-8 infection in genetically susceptible patients. 8 KS is classified into four types: classic, endemic, immunosuppression-associated or iatrogenic and AIDS-associated or epidemic. 13 Association of pemphigus (mainly PV) and KS has been previously reported. 14 In fact, pemphigus-associated KS is regarded as an iatrogenic disorder, develops after receiving immunosuppressive therapy, mainly corticosteroids. 14-16 However, rituximab-induced KS in HIVnegative patients (but not pemphigus patients), though as an extremely rare condition, have been previously reported. 17 Results of the recent cohort study showed that half of pemphigus-associated KS cases developed their KS lesions before the start of immunosuppressive therapy that is fairly in favor of the role of HHV-8 infection as a triggering factor in patients with pemphigus. 22 However, these findings can be explained by considering KS as a result of Koebner phenomenon in patients with latent HHV-8 infection. 26 According to the above-mentioned study, patients who devel- tumor regression in some cases, 32 this may not always be feasible due to intractable nature of pemphigus in some patients. Hence, maintaining a suitable level of immunosuppression to sustain a balance between therapeutic and adverse effects of treatment in order to having both of diseases under controlled, is sometimes challenging and hard to achieve. As mentioned before, the occurrence of the second and third KS lesions in our case was 1 month after tapering off the prednisolone. This would challenge the theory considers the withdrawal of immunosuppressant agents as the best therapeutic modality in patients with pemphigus. 32 In conclusion, we reported a case of KS with an unusual presentation to emphasize the fact that careful examination and clinical suspicion are the key factors for correct diagnosis. In fact, throat burning and odynophagia in PV patients might not be merely due to pemphigus erosions and should raise the suspicion of occurrence of other pathologic processes such as KS even in HIV-negative patients.
Furthermore, we highlighted the fact that not all of patients with pemphigus-associated KS have fulminant course. Therefore, the crucial question to be resolved is how we can discriminate between steroid-associated KS and disease-associated KS in patients with pemphigus.
Implementing some proceedings such as skin tuberculin test writingreview and editing (equal).

ACKNOWLEDGMENTS
The study was performed at the Autoimmune Bullous Diseases Research Center, Razi Hospital, Tehran, Iran.