Paraneoplastic Pemphigus/Paraneoplastic Autoimmune Multiorgan Syndrome: Part II. Diagnosis and Management.

In the second part of this Continuing Medical Education article on paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome (PNP/PAMS), its diagnostic criteria, investigative work-up, and management are reviewed. PNP/PAMS is a rare autoimmune blistering disorder associated with high morbidity and mortality. Recognizing PNP/PAMS's key features and its diagnostic criteria is critical in initiating appropriate work-up. Evaluating PNP/PAMS requires knowledge of its findings on histopathology, direct immunofluorescence, indirect immunofluorescence, and enzyme-linked immunosorbent assay. Lastly, treatments for PNP/PAMS are reviewed with suggestions based on case reports and expert opinions in the literature. LEARNING OBJECTIVES: After completing this learning objective, the reader will be able to identify the criteria necessary for diagnosing paraneoplastic pemphigus (PNP/PAMS), learn how to work-up a diagnosis of PNP/PAMS, and understand important principles in the management of PNP/PAMS.

Paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome: Part I. clinical overview and pathophysiology.

Paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome (PNP/PAMS) is a highly fatal autoimmune blistering disease. The condition occurs in patients with underlying benign or malignant neoplasms, most commonly lymphoproliferative disorders. Both humoral and cell-mediated immunities contribute to the pathogenesis, and autoantibodies against plakin family proteins are characteristic. Patients typically present with severe stomatitis and polymorphous skin lesions, which are often resistant to treatment. Bronchiolitis obliterans (BO) is a frequent complication which contributes to the high mortality rate of PNP/PAMS. Given the rarity of this disorder and heterogeneity of clinical presentation, clinicians should maintain a high index of suspicion for PNP/PAMS to avoid delayed diagnosis. In this first part of a two-part continuing medical education (CME) series, risk factors, pathogenesis, and clinical features of PNP/PAMS are discussed.

Errors encountered in the diagnostic pathway: A prospective single-institution study.

BACKGROUND: Biopsy specimens go through a diagnostic pathway before a pathology report is rendered for the clinician. Errors can occur at any step in this pathway. METHODS: A 1-year prospective study was conducted at a single academic institution to identify and characterize errors that occurred in the diagnostic pathway from the clinic to the dermatopathology lab. RESULTS: A total of 25 662 specimens were processed and 190 errors were recorded (an error rate of 0.7%). The most common errors were an incorrect biopsy site (n = 65), incorrect data entry of a correct diagnosis (n = 25), and specimen mix-up (n = 23). There were 17 diagnostic errors. Errors most often occurred in the pre-analytical phase (n = 128). The clinician was responsible for 34.2% of errors, the dermatopathologist for 23.7%, and the histotechnician for 18.9%. Slips were the most common type of human error (n = 156). CONCLUSION: The most common error involved an incorrect biopsy site at the clinical stage. Over two-thirds of errors occurred before the slide reached the dermatopathologist. Diagnostic errors (analytical phase) rarely occurred, and when they did occur, the clinician was most likely to discover the error. Examining and addressing common laboratory errors help to reduce their incidence and lead to quality improvement in dermatopathology.

Lichen Sclerosus of the Lip.

In this case report, we outline a case of a 36-year-old woman who presented to the dermatology clinic with a history of a hypopigmented macule on her lip. After conducting hepatitis C antibody testing and a shave biopsy, the patient was diagnosed with lichen sclerosus. Because of the increased risk for squamous cell carcinoma, she underwent an anogenital exam, where no lesions were found.

Vesiculobullous Diseases.

A diverse range of inflammatory dermatoses are characterized by vesicles or bullae [...].

Annular bullous diseases.

Annular bullous dermatoses represent an etiologically diverse group of cutaneous phenomena that present with a figurate morphology in association with vesicles and bullae. This group of diverse conditions consists of bullous pemphigoid; pemphigoid gestationis; epidermolysis bullosa simplex, Dowling-Meara type; linear immunoglobulin A bullous dermatosis; chronic bullous disease of childhood; anti-p200 pemphigoid; subcorneal pustular dermatosis; and immunoglobulin A pemphigus. Astute examination of clinical, histopathologic, and serologic features is crucial in distinguishing these bullous dermatoses. We review the clinical presentation, pathophysiology, histopathology, and treatments for each bullous annular disease to aid physicians in their recognition, diagnosis, and management.

Pustular Psoriasis and Acute Generalized Exanthematous Pustulosis.

The similarity between pustular psoriasis (PP) and acute generalized exanthematous pustulosis (AGEP) poses problems in the diagnosis and treatment of these two conditions. Significant clinical and histopathologic overlap exists between PP and AGEP. PP is an inflammatory disorder that has numerous clinical subtypes, but all with sterile pustules composed of neutrophils. AGEP is a severe cutaneous adverse reaction that is also characterized by non-follicular sterile pustules. Clinical features that suggest a diagnosis of PP over AGEP include a history of psoriasis and the presence of scaling plaques. Histologically, eosinophilic spongiosis, vacuolar interface dermatitis, and dermal eosinophilia favor a diagnosis of AGEP over PP. Importantly, PP and AGEP vary in clinical course and treatment. PP treatment involves topical steroids, oral retinoids, and systemic immunosuppressants. Newer therapies targeting IL-36, IL-23, IL-1, and PDE-4 have been investigated. The removal of the offending agent is a crucial part of the treatment of AGEP.

Bullous Pemphigoid and Other Pemphigoid Dermatoses.

The pemphigoid family of dermatoses is characterized by autoimmune subepidermal blistering. The classic paradigm for pemphigoid, and the most common member, is bullous pemphigoid. Its variable clinical presentation, with or without frank bullae, is linked by significant pruritus afflicting the elderly. Mucous membrane pemphigoid is an umbrella term for a group of subepidermal blistering dermatoses that favor the mucosal membranes and can scar. Epidermolysis bullosa acquisita is a chronic blistering disorder characterized by skin fragility, sensitivity to trauma, and its treatment-refractory nature. Clinicians that encounter these pemphigoid disorders may benefit from an overview of their clinical presentation, diagnostic work-up, and therapeutic management, with an emphasis on the most frequently encountered pemphigoid disease, bullous pemphigoid.

An Updated Review of Pemphigus Diseases.

Clinicians may encounter a variety of skin conditions that present with vesiculobullous lesions in their everyday practice. Pemphigus vulgaris, pemphigus foliaceus, IgA pemphigus, and paraneoplastic pemphigus represent the spectrum of autoimmune bullous dermatoses of the pemphigus family. The pemphigus family of diseases is characterized by significant morbidity and mortality. Considering the risks associated with a delayed diagnosis or misdiagnosis and the potential for overlap in clinical features and treatment, evaluation for suspected pemphigus disease often requires thorough clinical assessment and laboratory testing. Diagnosis is focused on individual biopsies for histopathology and direct immunofluorescence. Additional laboratory methods used for diagnosis include indirect immunofluorescence and enzyme-linked immunosorbent assay. Recent advancements, including anti-CD20 therapy, have improved the efficacy and reduced the morbidity of pemphigus treatment. This contribution presents updates on the pathophysiology, clinical features, diagnostic work-up, and medical management of pemphigus. Improved strategies for diagnosis and clinical assessment are reviewed, and newer treatment options are discussed.

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Review of Diagnosis and Management.

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are rare diseases that are characterized by widespread epidermal necrosis and sloughing of skin. They are associated with significant morbidity and mortality, and early diagnosis and treatment is critical in achieving favorable outcomes for patients. In this scoping review, Excerpta Medica dataBASE and PubMed were searched for publications that addressed recent advances in the diagnosis and management of the disease. Multiple proteins (galectin 7 and RIP3) were identified that are promising potential biomarkers for SJS/TEN, although both are still in early phases of research. Regarding treatment, cyclosporine is the most effective therapy for the treatment of SJS, and a combination of intravenous immunoglobulin (IVIg) and corticosteroids is most effective for SJS/TEN overlap and TEN. Due to the rare nature of the disease, there is a lack of prospective, randomized controlled trials and conducting these in the future would provide valuable insights into the management of this disease.

Differentiating Pemphigus Foliaceus From Pemphigus Vulgaris in Clinical Practice.

Pemphigus is a skin condition that causes intraepidermal separation of keratinocytes. Multiple types of pemphigus exist, including pemphigus vulgaris and pemphigus foliaceus. These can be differentiated by histopathology, clinical presentation, appearance of lesions, and antibodies, among other factors. It is important to distinguish between the two because of differences in management and prognosis. Here we present a case of pemphigus foliaceus, as well as a discussion of the key differences between pemphigus foliaceus and vulgaris.

Glomangioma of the elbow.

We present a patient with a painful, mobile nodule on the elbow. The nodule was skin-colored and had no punctum or discharge. It was excised and histopathology showed that the lesion was a glomangioma, or glomuvenous malformation. This is a neoplasm that arises from the glomus body, a thermoregulatory neurovascular structure. The glomus body is composed of glomus cells, vascular cells, and smooth muscle cells. Three subtypes of neoplasms may arise from the glomus body, depending on the extent to which they involve the three types of cells. They include glomus tumors, glomangiomas/glomuvenous malformations, and glomangiomyomas. This case was unusual in that it did not present with surface color change to indicate a vascular component.

Paraneoplastic pemphigus: Revised diagnostic criteria based on literature analysis.

BACKGROUND: Paraneoplastic pemphigus (PNP) is a rare autoimmune bullous disease classically associated with an underlying neoplasm. The heterogeneous clinical and histopathologic features of the disease make diagnosis challenging for clinicians. There are no formally accepted diagnostic criteria, and newer techniques for identifying antibodies directed against plakin proteins have largely replaced immunoprecipitation, the historic gold standard. METHODS: An analysis of 265 published cases of PNP was performed. The clinical, histopathologic, and immunologic features of PNP were assessed. RESULTS: Based on this review, we modified previous diagnostic criteria to capture 89.4% of PNP cases compared to 71.2% of cases captured by the most commonly referenced criteria devised by Camisa and Helm (p-value < 0.01, z-test; 95% CI [10.2, 33.6]). CONCLUSION: These revised diagnostic criteria address the variable clinical, histopathologic, and biochemical features of PNP, allowing physicians to have greater confidence in diagnosis of this rare and often fatal disease. The revised criteria include three major criteria and two minor criteria, whereby meeting either all three major criteria or two major and both minor criteria would fulfill a diagnosis of paraneoplastic pemphigus. The major criteria include (a) mucous membrane lesions with or without cutaneous involvement, (b) concomitant internal neoplasm, and (b) serologic evidence of anti-plakin antibodies. The minor criteria include (a) acantholysis and/or lichenoid interface dermatitis on histopathology and (b) direct immunofluorescence staining showing intercellular and/or basement membrane staining.