UPMC Dermatopathology “Case of the Month” Presentations
UPP - Department of Dermatology, Dermatopathology Unit
Case Author: Matthew Zirwas, MD Case Sponser: nnnn, MD
SEPTEMBER 2003 CASE OF THE MONTH
DISCUSSION & DIAGNOSIS
This patient presented both diagnostic and therapeutic dilemmas at the time of presentation. From a diagnostic perspective, two main entities were considered – Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis overlap (SJS/TEN overlap) was the leading consideration, but paraneoplastic pemphigus (PP) was also a reasonable consideration at the time of presentation.
Paraneoplastic pemphigus is an autoimmune blistering disorder seen in patients with malignancies. The most characteristic clinical findings are severe, intractable stomatitis and lichenoid, bullous, or erythema multiforme-like cutaneous lesions. The most commonly associated malignancies are non-Hodgkins lymphoma, chronic lymphocytic leukemia, and Castleman’s disease. Adenocarcinomas and squamous cell carcinomas are extremely uncommonly associated with paraneoplastic pemphigus. PP also has a relatively specific histopathologic and immunofluorescent pattern on skin biopsy. The histolopathologic pattern is often polymorphic, showing interface dermatitis, keratinocyte necrosis, and acantholysis.1 The direct immunofluorescence pattern consists of both intercellular and basement membrane zone deposition of IgG, and on indirect immunofluorescence, patient’s sera reacts with rat bladder epithelium.1
Stevens-Johnson syndrome and toxic epidermal necrolysis are severe mucocutaneous drug reactions which result in epidermal necrosis and mucous membrane erosions. A recently validated classification system defined this spectrum of diseases based on clinical findings (Table 1) . Many different medications have been implicated in various cases, but the medications with the highest risks are sulfonamide antibiotics and anti-convulsant agents. Risk is greatest early during therapy, and is concentrated in the first two months of therapy with any given agent.
At the time of admission, the diagnoses of SJS/TEN overlap syndrome and paraneoplastic pemphigus were both considered. Given the relatively mild severity of the stomatitis and the low association of paraneoplastic pemphigus with squamous cell carcinomas, SJS/TEN overlap was strongly favored. Skin biopsy with direct immunofluorescence was performed at the time of admission to confirm the diagnosis.
Estimation of prognosis at the time of admission is frequently difficult in cases of TEN/SJS. A scoring system called SCORTEN has been developed and validated. Seven items are included in SCORTEN, and one point is added for each variable that is present. Prognosis is then based on the total number of points (Table 2). Based on this scoring system, our patient had a SCORTEN of 3 (one point each for age over 40, presence of malignancy, and elevated serum glucose) with a predicted mortality of 35.3%.
Initial management was instituted based on the working diagnosis of SJS/TEN overlap, with significant concern that the clinical picture would quickly evolve into full TEN.
Management of SJS and TEN has several components. It is generally accepted that immediate cessation of the causative agent and supportive care are the cornerstones of management. Supportive care includes themoregulatory support, aggressive management of fluids and electrolytes, nutritional support, treatment of infection (if suspected), ophthalmology consultation, and appropriate wound care.
Specific treatment of TEN and SJS/TEN overlap is more controversial. Several treatments have shown promise in small trials and case reports. These include cyclosporine, cyclophosphamide, plasmapheresis, and n-acetylcystein.6 However, none of these agents have been evaluated in larger trials.
The most promising recent development in the treatment of TEN has been intravenous immunoglobulin (IVIG). An initial study in ten patients showed remarkable improvement following the administration of IVIG. This article suggested that the likely mechanism of action of IVIG was blockade of the Fas-Fas Ligand interaction. Subsequently, three more studies of IVIG in the treatment of TEN have been published. Two of these studies (encompassing 56 total patients) showed a significant improvement in survival when IVIG was administered compared to anticipated survival if IVIG had not been administered. , However, a third trial, which included 34 patients, showed no survival benefit with IVIG administration, and instead showed an excess number of mortalities compared to what would be expected if IVIG had not been administered.
Given the conflicting data on the utility of IVIG, and other specific therapies for TEN and SJS, we elected to manage our patient with supportive care and withdrawal of etiologic medication only. Our patient did remarkably well over the next 7 days. Progression of his skin disease halted after discontinuation of the carbamazepine and he made a full recovery without any specific therapy directed at the TEN/SJS.
References
Joly P, Richard C, et al. Sensitivity and specificity of clinical, histologic, and immunologic features in the diagnosis of paraneoplastic pemphigus. J Amer Acad Derm 2000; 43:619-626.