Paraneoplastic pemphigus presenting as a prodrome to aggressive T cell lymphoma.

Paraneoplastic pemphigus (PNP) is a rare disease with an unclear mechanism of pathogenesis. We present a case of a male patient who presented with wound management after being diagnosed with Castleman disease-associated paraneoplastic pemphigus (PNP). The patient's condition was not improving; as a result, extensive workup was repeated, which confirmed the diagnosis of aggressive T cell lymphoblastic lymphoma. Our case signifies the importance of keeping a high index of suspicion for PNP-associated malignancies. This case report also adds emphasis to the diagnostic challenges faced by clinicians, making clinical correlation with multidisciplinary approach essential. Therefore, if clinically indicated, we need to revisit the diagnosis and seek alternative explanations to prevent delays in management.

Direct medical cost related to the management of pemphigus: A pilot Tunisian study.

INTRODUCTION: Pemphigus is a therapeutically challenging disease with high morbidity and economic burden. First-line prescription of rituximab remains limited in Tunisia due to its high cost. Systemic steroids remain the standard of care but are associated with a major risk of morbidities and higher treatment costs. AIM: To assess the direct medical costs of pemphigus in Tunisia. METHODS: Retrospective estimation of direct medical costs during the 18 months following the diagnosis using the "bottom-up approach" in the Dermatology Department of Hedi Chaker Hospital, Sfax, Tunisia. RESULTS: Total medical costs were estimated at 38745.7 €, with an average cost of 1 210 € per patient and per year: paraclinical investigations (46%), medical treatment (30%), hospitalization (21%) and outpatient visits (3%). The average cost was the highest in the age group of 15-24 years (1553 €). Treatment costs related to corticosteroid-induced morbidity were estimated at 1208 €. CONCLUSIONS: The management of pemphigus in Tunisia needs to be adapted to take into account the health economic analysis in order to reduce overall disease costs and the burden of steroid-induced morbidities.

Concordance of clinical, histopathologic and direct Immunofluorescence findings in patients with intraepidermal immunobullous disorders.

Objective: To determine the concordance among clinical, histopathological and immunofluorescence as diagnostic methods for intraepidermal immunobullous disorders. METHODS: The prospective cross-sectional study was conducted at the Institute of Skin Diseases, Karachi, from December 2020 to December 2022, and comprised adult patients of either gender presenting with complaints of bullae, vesicles, pustules and crusts on the skin or mucous membrane. Diagnostic findings of each patient as obtained by clinical assessment, microscopy and direct immunofluorescence were compared. Data was analysed using SPSS 19. RESULTS: Of the 81 patients, 41(50.6%) were males and 40(49.4%) were females. The overall median age was 35 years (interquartile range: 23 years), with 66(75%) patients aged 19-55 years. The predominant body site involved was the trunk 49(60.5%), followed by mucosa 26(32.1%). Clinical diagnosis detected 80(98.7%) cases, compared to 76(93.8%) by microscopy and 81(100%) by direct immunofluorescence. Conclusion: Direct immunofluorescence was found to be the gold standard for a confirmatory diagnosis of intraepidermal immunobullous disorders, especially when clinical and histopathology findings were inconclusive.

Direct immunofluorescence (DIF) versus immunohistochemical (IHC) staining of complements and immunoglobulins (Ig) in pemphigus group.

INTRODUCTION: Pemphigus is a group of bullous disorders of the skin characterized by the formation of autoantibodies present in the intercellular junction of the epidermis. Diagnosis is made by clinical, histopathological examination, and DIF. As DIF needs frozen sections, fluorescent tagged antibodies, UV light microscope for examination, and trained personnel, its non-availability makes a definitive diagnosis challenging. AIMS AND OBJECTIVES: To evaluate the utility of IHC staining of complements and Ig in cases of Pemphigus. MATERIALS AND METHODS: Twenty-six diagnosed cases of Pemphigus were stained by Peroxidase immunohistochemical method using monoclonal antibody to IgG, IgA, IgM, IgG4, C3, C4 d with DAB as chromogen. Pemphigus cases include twenty of pemphigus vulgaris (PV), four cases of pemphigus foliaceous (PF), and two of pemphigus vegetans (Pveg). Positivity was defined as the deposition of Ig and complements as distinct, continuous brown staining of keratinocytes at intercellular junctions. RESULT: On IHC total of 20 PV 17 showed positivity (85%) for IgG, 11 (55%) C4d, 19 (95%) C3d, and 16 (80%) IgG4 deposits at the intercellular junction of the epidermis. All cases of PF showed a deposit of IgG, with three (75%) cases for IgG4, C3d, and C4d. Both cases of Pveg showed positivity for IgG and C4d while one case was negative for IgG4 and C3d. The overall IgG, C3, IgG4, and C4d expression for pemphigus was seen in 88%, 88%, 76.9%, and 61.5% of cases. The relation between these markers, combination of IgG and C3, was best related to each other ( P value = 0.80). The sensitivities for IgG, IgG4, and C3 were 77.8%%, 73%, and 73% resp. CONCLUSION: We conclude that IHC is a useful tool in the diagnosis of PV with the highest sensitivity of IgG and C3d. The combination of IgG and C3d could replace the DIF in almost all of our cases, so IHC on FFPE sections be used as an alternative method to DIF.

Pemphigus Vulgaris Successfully Treated With Bromocriptine.

Pemphigus vulgaris (PV) is an autoimmune blistering skin condition primarily treated with immunosuppressive agents. We describe a case of PV successfully treated with nonconventional treatment, bromocriptine mesylate. Bromocriptine has been used in human trials showing beneficial therapeutic effects in managing autoimmune conditions. The results from experimental trials and the low toxicity of bromocriptine in comparison with immunosuppressive agents form a solid rationale for investigating its role in controlling PV.  J Drugs Dermatol. 2024;23(3):     doi:10.36849/JDD.7720e.

Comparing Clinical Outcomes of Steroid-Sparing Therapy With Rituximab Versus Rituximab Alone in Pemphigus.

BACKGROUND: Previous clinical trials have demonstrated that rituximab therapy combined with conventional steroid-sparing therapy (SST) has increased rates of disease control for mucous membrane pemphigoid compared with rituximab alone. However, limited data is available regarding the role of SST with rituximab therapy in pemphigus. OBJECTIVE: This study aimed to examine clinical outcomes in pemphigus patients treated with rituximab with SST versus without the addition of SST. METHODS: A retrospective chart review was performed for adult pemphigus patients in the Southeastern US at Emory between January 1, 2011, and December 31, 2021. Primary outcomes, including time to remission, time to prednisone dose of 10 mg or less, time to cessation of prednisone therapy, and time to relapse after a rituximab cycle, were compared between patients on SST and patients without SST.  Results: Following rituximab therapy, there was no difference in time to remission, time to prednisone dose of 10 mg or less, time to cessation of prednisone therapy, or time to relapse for patients with or without SST. LIMITATIONS: Our study is limited by its retrospective decline, setting at a single academic center, and inclusion of a high proportion of patients with moderate disease. CONCLUSIONS: The use of SST with rituximab dosing did not improve clinical outcomes related to time to remission, reduction in prednisone dosing, or relapse. These data provide further evidence for the use of rituximab in the majority of pemphigus patients without the need for SST. J Drugs Dermatol. 2024;23(3):e97-e99    doi:10.36849/JDD.7949e.

Immune-mediated oral mucosal pathology: a comprehensive review and update for clinicians - part II.

The oral mucosa can be involved in a wide variety of mucocutaneous conditions that may present primarily in the mouth or affect other cutaneous or mucosal sites. Many of these conditions are immune mediated and typically present as inflammatory mucosal pathology. Patients experiencing such conditions usually seek medical evaluation and treatment due to the associated pain and discomfort, and occasionally taste disturbance or dysphagia and the overall deterioration in the oral health-related quality of life. These conditions share some common features and there could be some overlap in their clinical presentation, which can lead to delays in diagnosis and proper management of patients. Clinicians dealing with such disorders, including dermatologists, need to be aware of the oral manifestations of mucocutaneous conditions, their clinical features, underlying mechanisms, diagnostic approaches, and treatment options, as well as the recent advances in the research on these conditions. This review provides a comprehensive, evidence-based reference for clinicians, with updated insights into a group of immune mediated conditions known to cause oral mucosal pathology. Part one will cover oral lichen planus, erythema multiforme and systemic lupus erythematosus, while part two will cover recurrent aphthous stomatitis, pemphigus vulgaris and mucous membrane pemphigoid, in addition to the less common disorders linear IgA disease, dermatitis herpetiformis and epidermolysis bullosa.

Superficial and Bullous Neutrophilic Dermatoses: Sneddon-Wilkinson, IgA Pemphigus, and Bullous Lupus.

Sneddon-Wilkinson disease (SWD), IgA pemphigus, and bullous systemic lupus erythematosus (BSLE) are superficial and bullous neutrophilic dermatoses. They are all characterized by sterile neutrophilic infiltrate but differ in the level of skin affected and presence of autoantibodies. Both SWD and IgA pemphigus present with grouped flaccid pustules and have epidermal involvement; it is unclear whether they are distinct or exist on a spectrum of the same disease. IgA pemphigus is distinguished from SWD by positive direct immunofluorescence showing intercellular IgA deposition. BSLE presents with tense bullae, dermal neutrophilic infiltrate, and direct immunofluorescence showing linear IgG deposition along the dermal-epidermal junction.

Evaluation of Dry Eye Severity and Ocular Surface Inflammation in Patients with Pemphigus and Pemphigoid.

PURPOSE: To evaluate ocular surface involvement, tear cytokine levels, and histopathological changes in pemphigus and pemphigoid patients. METHODS: A total of 22 patients (15 pemphigus and 7 pemphigoids) and 21 non-diseased controls were enrolled in our study. All participants underwent ocular surface evaluation, which included ocular surface disease index test, slit lamp observation, dry eye-related examination, tear multicytokine analysis, and conjunctival impression cytology. RESULTS: Pemphigus and pemphigoid patients presented much more severe conjunctivochalasis, corneal epithelial defects, corneal opacity, symblepharon   and dry eye. Severe ocular surface squamous metaplasia and a significant increase of tear macrophage inflammatory protein-1beta, tumor necrosis factor-alpha, interleukin (IL)-1ß, IL -6, and IL-8 occurred in pemphigus and pemphigoid patients. CONCLUSIONS: Our results revealed that ocular surface inflammation and dry eye persist in most pemphigus and pemphigoid patients, and do not occur in parallel with the systemic course. Regular ophthalmological examinations and local anti-inflammatory should be provided for pemphigus and pemphigoid patients.

Is it Possible to Obtain Immunofluorescence Data in Formalin-Fixed Paraffin-Embedded Skin Samples for the Diagnosis of Pemphigus Vulgaris and Bullous Pemphigoid.

OBJECTIVE: The gold-standard method for assessment of autoimmune bullous disease is direct/indirect immunofluorescence (IF) examination applied to fresh frozen tissue. Since the sensitivity of IF is greatly reduced in formalin-fixed paraffin-embedded (FFPE) tissues, IF cannot be relied upon in these samples. However, immunohistochemistry with the C4d antibody is a promising marker used as a surrogate for immune complex deposition, in nephropathology practice, and the paraffin IF method is also used as a `salvage` technique when fresh frozen tissue is not available or lacks glomeruli. We aimed to investigate whether it is possible to obtain immunofluorescence data from FFPE tissues diagnosed with bullous pemphigoid (BP) and pemphigus vulgaris (PV) and its relationship with inflammatory parameters in the skin. MATERIAL AND METHODS: Eighty-nine in-house cases with both IgG and C3 positivity by routine immunofluorescence examination were included in the study. Inflammation parameters were evaluated in hematoxylin-eosin sections. Immunofluorescence study with IgG protease digestion and C4d immunohistochemistry were performed. RESULTS: Results of 83 biopsies were obtained by paraffin immunofluorescence with IgG. There were positive reactions in 28 (34%) of these 83 biopsies. Five of the 28 positive results belonged to BP (18%), and 23 were PV (82%). Ten positive results were on lesional skin (36%), and 18 (64%) were on non-lesional skin. In the immunohistochemical study with C4d, 84 biopsy results were obtained. There were positive reactions in 34 (40.4%) of 84 biopsies. Of the 34 positive results, 12 belonged to BP (35.3%) and 22 to PV (64.7%). Again, 22 (64.7%) of 34 positive results belonged to lesional skin, and 12 (35.3%) belonged to non-lesional skin. When both techniques were used together, 44 (54%) of 81 biopsies yielded positive results for at least one of the two studies, while in 37 (46%), both tests showed negative results. CONCLUSION: The sensitivity of both IgG and C4d was less than in the literature, especially in BP-diagnosed biopsies. Positive samples were mostly PV. In conclusion, obtaining immunofluorescence data in FFPE samples is possible and is independent of the related skin being lesional or not, however, negative results should not be relied upon.