Presentations

Abstract

Introduction: Amyloidosis is the extracellular deposition of mutated proteins consisting of insoluble amyloid fibrils in the body [1]. This condition can further be subdivided into systemic and localized forms affecting either multiple organ systems or being limited to a single organ. Systemic forms include primary amyloidosis in cases such as plasma cell dyscrasias (i.e. multiple myeloma), secondary amyloidosis which is associated with chronic diseases such as inflammatory or infectious processes, dialysis related and transthyretin amyloidosis [2]. Bullous amyloidosis a rare condition that can present as cutaneous lesions representing an underlying systemic process such as AL amyloidosis. We present a case of a gentleman previously diagnosed with bullous pemphigoid presenting with a new oral lesion.

Case Information: A 75-year-old gentleman presents as a new patient for primary care visit after moving from Peru a few months ago. His past medical history included prostate cancer status post prostatectomy and bullous pemphigoid which was treated with steroids and tacrolimus. In clinic he presented with a new oral lesion that he noted 3-5 months ago. He noted oral cavity pain at the base of his tongue without any dyspnea or dysphagia. He endorsed rare alcohol use and denied any history of smoking or new medication changes. Physical exam was notable for macroglossia, and he was found to have a tender 4mm ulcer in the right retromolar trigone region associated with surrounding leukoplakia. On presentation his vital signs were stable, and CBC revealed macrocytic anemia. CMP was unremarkable. After being referred and evaluated by ENT, he underwent biopsy of the oral ulcer, and the pathology report revealed areas of amorphous debris within the submucosal tissues that were positive for amyloid by Congo Red staining under polarized light. This sample was further sent for amyloid subtyping which did express IgG. Chromogenic in situ hybridization stains revealed that plasma cells demonstrated a strong kappa light chain expression with some background lambda light chain expression. These findings were consistent with bullous amyloidosis. Since bullous amyloidosis is often related to AL amyloid, an underlying plasma cell dyscrasia work-up was started in clinic. This revealed a protein electrophoresis with a monoclonal band in the mid-gamma region, increased serum free lambda light chains and immunofixation with a faint band of free lambda chains and lambda IgG migration. Echocardiogram did not show evidence of amyloidosis. Given these findings and concern for IgG gammopathy, he was sent a referral for evaluation by hematology/oncology. He was then scheduled for bone marrow biopsy and referred to stem cell transplant physician for further management. Due to the rarity of cases of bullous amyloidosis, there are few set guidelines regarding treatment. Of the patient cases described in the literature, many were treated for the underlying malignancy i.e. multiple myeloma associated amyloidosis which consisted of cyclophosphamide, bortezomib and dexamethasone. [4]

Discussion/Clinical Findings: Primary systemic amyloidosis can present with mucocutaneous lesions 30 to 40% of the time which include skin thickening, plaques, purpura, nodules or bullae (3). Bullous amyloid is a rare amyloidosis phenomenon with few reported cases. It is thought that the amyloid deposits in capillaries which weaken blood vessel walls forming bullae secondary to friction or trauma [3]. This can be an exceedingly difficult diagnosis to make as multiple and more common dermatological conditions can present with similar blistering skin lesions. This includes bullous pemphigoid, porphyria cutanea tarda, epidermolysis bullosa, drug induced bullous reactions, IgA disease and pseudoporphyria [3]. Correct and timely diagnosis is crucial as bullous amyloid is often associated with an underlying plasma cell dyscrasia such as multiple myeloma. Clinical features such as macroglossia can also be a physical exam finding associated with bullous amyloidosis as seen in this patient's case. Our patient who was previously diagnosed with bullous pemphigoid presented with an ulcerated oral lesion with leukoplakia which is atypical of bullous pemphigoid as it usually spares the oral cavity and manifests with tense blisters. This prompted further investigation with a biopsy that led to the diagnosis bullous amyloid and further work up concerning for IgG gammopathy. It is important that clinicians challenge pre-existing diagnoses especially when a patient presents with new symptoms or atypical findings. In this case a previously thought diagnosis of bullous pemphigoid was later revealed as bullous amyloidosis associated with an underlying a plasma cell dyscrasia which caused a delay in appropriate treatment.

Conclusion: Bullous amyloidosis is a rare disease that is associated with an underlying plasma cell dyscrasia. Unfortunately, these skin lesions are often misdiagnosed which can delay treatment for malignancy. It is important to recognize and keep different forms of cutaneous amyloidosis on one's differential particularly when patients present with atypical features or refractory symptoms.