Prompt Resolution of Refractory Pemphigus vulgaris Following Removal of a Pheochromocytoma: Case Report and Overview of Putative Pathophysiologic Mechanisms

Presentation Number: SAT 393
Date of Presentation: April 1st, 2017

Zeina Carolina Hannoush*1, Juan Diego Palacios2, Oren Lifshitz3, John I Lew1 and Alejandro Raul Ayala4
1University of Miami Miller School of Medicine, Miami, FL, 2UNIVERSITY OF MIAMI/JACKSON MEMORIAL HOSPITAL, Miami, FL, 3Private practice, miami, 4University of Miami, Miami, FL

Abstract

Background

 

Pemphigus vulgaris is an epidermal disease affecting the skin and mucous membranes caused by autoantibodies to the desmosomal protein desmoglein ultimately resulting in acantholysis and blistering with complement activation and release of inflammatory mediators [1]. Multiple studies suggest that non-neuronal adrenergic/cholinergic systems play a pathophysiologic role in several dermatoses, including pemphigus [2]. Pheochormocytomas are catecholamine-secreting tumors that arise from chromaffin cells of the adrenal medulla leading to a hyperadrenergic state.

Case Presentation

 

The patient is a 39 year-old female with new onset hypertension, palpitations panic attacks, anxiety and headaches. She had history of pemphigus vulgaris diagnosed by skin biopsy revealing intraepidermal acantholysis and linear/granular IgG and C3 antibody epithelial surface deposits on immunofluorescence with no IgA or IgM antibodies. She was treated with mycophenolate mofetil without adequate response. She underwent a CT of the abdomen for evaluation of nephrolithiasis  that revealed a 3.4 cm left adrenal tumor with no signal dropout on out of face imaging and high T2 weighted intensity strongly suggesting a pheochromocytoma. Hormonal evaluation revealed elevated 24 hour urine metanephrine 841 mcg/24h (normal <190 mcg/24h), normetanephrine 1192 mcg/24h (normal < 482 mcg/24h) and total metanephrines 2033 mcg/24h (normal < 695 mcg/24h). Aldosterone, renin, TSH, comprehensive metabolic profile and urine free cortisol where unrevealing. Her PTH was elevated at 81 pg/mL, calcium of 10.1 mg/dL, with normal phosphorus, albumin and vitamin D level. The diagnosis of normocalcemic hyperparathyroidism was entertained raising the question of a multi-gland neoplastic syndrome currently under investigation.

The patient underwent successful laparoscopic left adrenalectomy. Pathology revealed a left 3.8 cm pheochromocytoma. Within a week, her blood pressure normalized and surprisingly, her pemphigus spontaneously resolved.

Discussion and conclusions

 

Multiple studies suggest that the epidermal-adrenergic/cholinergic signal pathway controls calcium homeostasis, cell growth, differentiation, motility and pigmentation via B2 and a1 adrenoreceptors [2]. In addition, patients with may also have anti acetylcholine receptor antibodies [3]. Research in mice has shown that these non-desmoglein antibodies can induce pemphigus-like lesions [4].

These findings, along with the striking clinical improvement seen in our patient suggest that catecholamines may play an important role in the pathophysiology of pemphigus vulgaris. Paraneoplastic pemphigus has been described associated with multiple types of tumors [5-7]. To the best of our knowledge this is the first case report of refractory pemphigus spontaneously resolving after resection of a pheochromocytoma.

 

Disclosure: ARA: Advisory Group Member, Novartis Pharmaceuticals, Consultant, NHT theapeutics. Nothing to Disclose: ZCH, JDP, OL, JIL