TEMPI syndrome: A clinical, light-microscopic and phenotypic evaluation with review of the literature.

BACKGROUND AND OBJECTIVES: TEMPI (telangiectasias, elevated erythropoietin and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonaryshunting) syndrome is a rare multisystemic disease classified as a monoclonal gammopathy of cutaneous significance. The pathogenesis and etiology of TEMPIare not well known because of the rarity of this disorder. Although telangiectasias are the hallmark of this syndrome, skin biopsies are rarely performed. We aim to further characterize TEMPI syndrome through the evaluationof a skin biopsy. METHODS: We reviewed the histopathology and immunophenotypic profile of a skin biopsy from a 53-year-oldwoman diagnosed with TEMPI syndrome. Other components of her syndromic complex included an IgA myeloma, elevated vascular endothelial growth factor (VEGF), and erythrocytosis. RESULTS: A biopsy showed prominent vascular ectasia with some degree of microvascular basement membranezone thickening. Our patient had a reduction in neoplastic plasma cell burdenand clearing of her telangiectasias following myeloma directed treatment. CONCLUSIONS: TEMPI can beviewed as a reactive vascular paraneoplastic syndrome in the setting of a plasma cell dyscrasia. Elaboration of VEGF from neoplastic plasma cells is likely pathogenetically implicated and appears to be a common link that explains other vascular lesions associated with monoclonal gammopathy syndromes.

Tumor necrosis factor ALPHA Inhibitor Associated Köhlmeier-Degos Disease as a Novel Iatrogenic Paradigm That Underscores Excessive Type I Interferon in Its Pathogenesis.

ABSTRACT: Malignant atrophic papulosis/Köhlmeier-Degos disease was first described in 1941 by Köhlmeier in an anecdotal case report that described a young man who presented with extensive multiple intestinal perforations and a papular skin rash. Köhlmeier-Degos disease represents a unique vasculopathy targeting both the microvasculature and the arterial system. One of its most characteristic features is reflected by the discrete multifocal depressed porcelain lesions involving the skin and gastrointestinal tract. The pathological findings are striking and can be broadly categorized into those that are vascular in nature versus extravascular matrix production in the context of extensive extravascular hyaluronic acid and collagen deposition. A dynamic evolutionary morphology is observed not only clinically but also histologically. The microvascular alterations are particularly evident in the skin and are characterized by endothelial cell necrosis with subsequent endothelial cell detachment accompanied by intraluminal fibrin deposition, defining a thrombogenic microangiopathy that in later stage lesions is typically pauci-inflammatory. The arterial lesions are very distinctive and include significant neointimal proliferation with vascular luminal occlusion by amorphous plugs of collagen intimately admixed with platelets. Pathogenetically enhanced type I interferon signaling and endothelial cell injury mediated by the membranolytic attack complex (ie, C5b-9) are key in the evolution of the thrombotic microvascular and obliterative fibrosing arteriopathic changes. We describe a case of Köhlmeier-Degos disease that developed in the setting of tumor necrosis factor (TNF)-alpha inhibitor therapy with the drug golimumab. The clinical features, light microscopic findings, and a pathophysiologic paradigm based on the critical role of TNF-alpha in controlling the type I interferon response are discussed.

Febrile Ulceronecrotic Mucha-Habermann Disease Associated With Hemophagocytic Lymphohistiocytosis: A Case Report and Review of the Literature.

ABSTRACT: Mucha-Habermann disease (MHD) is an inflammatory skin disease characterized by polymorphous eruptions of erythematous, necrotic macules that have been reported for similarities to cutaneous T-cell lymphoma. Febrile ulceronecrotic MHD (FUMHD) represents a severe variant of MHD, marked by ulcers, hemorrhagic bullae, and systemic symptoms. Herein, we report a case of a severely atypical lymphomatoid expression of FUMHD associated with hemophagocytic lymphohistiocytosis (HLH). A previously healthy 21-year-old woman was admitted to the hospital with a rapidly progressive necrotic papular rash. Physical examination revealed right orbital swelling, bilateral hemorrhagic auricular bullae, and multiple ulcerative purpuric papulonodules on the trunk, face, and extremities. Biopsy indicated a dermal and subcutaneous infiltrate of atypical CD8 + lymphocytes with loss of CD5 and reduction in CD7 expression, along with features of lymphomatoid vasculitis. A diagnosis of a severely atypical lymphomatoid expression of FUMHD was made. The patient also met 7 of 9 HLH-2004 criteria, leading to a diagnosis of HLH. Positron emission tomography/computed tomography, flow cytometry, and rheumatologic workup were unremarkable. Treatment with an eight-week course of etoposide and dexamethasone for HLH led to rapid clinical improvement. Over time, her skin lesions regressed and eventually scabbed over to leave hyperpigmented scars, confirming the diagnosis of MHD. She has remained stable, off therapy for 4 years. Although potentially fatal, FUMHD often exhibits favorable outcomes and may resolve without recurrence, as in our patient. FUMHD should be considered in the differential diagnosis for patients presenting with cutaneous CD8 + necrotizing angiocentric lymphoproliferative disease complicated by HLH.

Cutaneous type IV hypersensitivity reaction following tebentafusp treatment for uveal melanoma.

Tebentafusp is a bispecific protein that recently underwent FDA approval for the treatment of metastatic uveal melanoma that functions by redirecting cytotoxic T cells to glycoprotein-100, a protein highly expressed in melanoma. Although clinical trials have demonstrated that rashes are common in the first few days of treatment, little is known about skin reactions that develop later in the treatment course. Herein, we describe a type IV hypersensitivity reaction and vitiligo-like depigmentation that developed six weeks into treatment and discuss the possible mechanisms underlying these reactions. The type IV hypersensitivity reaction resolved without intervention within seven weeks of onset, suggesting that tebentafusp can be safely continued in select patients who develop this cutaneous reaction.

Expanding the Differential Diagnosis of the Painful Nail: A Case of an Onychopapilloma with Neuroma.

Introduction: Onychopapilloma most commonly presents as longitudinal erythronychia, but diagnosis may be challenging in some cases due to varied clinical presentations. Most patients with onychopapillomas do not report associated pain but instead more commonly report functional interference. Case Report: We present a case of a 74-year-old female with a 5-year history of splitting and lifting of the right thumbnail, accompanied by nail sensitivity and intermittent painful throbbing. Clinical examination was significant for a less than 1 mm red line with distal onycholysis. Love's test and a cold test performed with ice pack were negative. X-ray of the right thumb was negative for erosion or exostosis. Nail biopsy was performed, and dermatopathology was consistent with onychopapilloma with a concomitant traumatic neuroma. Conclusion: We report a case of onychopapilloma with a concomitant traumatic neuroma. Subungual neuromas are extremely rare and have not previously been associated with onychopapilloma. Our case supports the expansion of the differential diagnosis for a painful nail and demonstrates the importance of diagnostic confirmation with biopsy and histopathology.

Progressive Dyspnea in a Woman With Tracheal Stenosis and Rheumatoid Arthritis.

CASE PRESENTATION: An 82-year-old woman with a remote tracheostomy due to vocal cord paralysis and long-standing erosive, seropositive rheumatoid arthritis (RA) well controlled with methotrexate sought treatment at the ED with 1 month of dyspnea, chest tightness, and cough productive of blood-tinged sputum. She had been treated unsuccessfully as an outpatient with multiple courses of antibiotics. She did not smoke or drink alcohol and had no recent travel outside the country. Given concern for airway compromise, she was admitted to the hospital.

Subcutaneous panniculitic-like T-cell lymphoma localized to a site of peginterferon alfa-2a administration.

T cell dyscrasias that demonstrate a proclivity for the subcutaneous fat include atypical lymphocytic lobular panniculitis, lupus profundus, and primary subcutaneous T cell lymphoma, including subcutaneous panniculitis-like T cell lymphoma (SPTCL). We encountered two patients who developed fever and indurated abdominal erythema at their peginterferon alfa-2a injection sites. Biopsies showed an atypical CD8 positive, granzyme positive, CD5 negative, MXA negative lymphocytic lobular panniculitis, diagnostic of SPTCL. Peginterferon alfa-2a was held in both patients. One patient received chemotherapy with an excellent response, while the other continued to have progressive disease. Peginterferon alfa-2a is known to significantly elevate serum MXA, which may induce high levels of MXA expression at the injection site, creating a microenvironment for the development of lupus profundus, which may eventuate into SPTCL. In summation, a potential risk of peginterferon alfa-2a injections is the development of SPTCL potentially arising in a background of an exogenous interferon triggered lymphocytic panniculitis.

Horrifying Basal Cell Carcinoma Presenting as Progressive Pyoderma Gangrenosum: Case Report.

Introduction: Skin ulcers can be challenging to diagnose and manage, particularly with comorbid autoimmune and gastrointestinal diseases. Occam's razor encourages the simplest explanation to guide care, but reconsideration must occur when intervention proves futile. Case Presentation: We report the case of a 70-year-old male, with a 17-year history of expanding pretibial skin ulcer, presumed by prior care providers to be pyoderma gangrenosum related to Crohn's disease. A surgical biopsy performed upon presentation to our institution revealed basal cell carcinoma of the skin, invasive to the proximal tibia with associated deep infection, prompting transfemoral amputation. Conclusion: This report is written as a reminder to reconsider a diagnosis and consider seeking additional expertise when a patient's condition progressively worsens despite intervention. Earlier diagnosis likely would have facilitated therapeutic limb salvage care.

Exploring cutaneous lymphoproliferative disorders in the wake of COVID-19 vaccination.

Background: Individual reports have described lymphoproliferative disorders (LPDs) and cutaneous lymphomas emerging after administration of the COVID-19 vaccine; however, the relationship between reactions and vaccine types has not yet been examined. Objective: Determine if there are cases of cutaneous LPDs associated with certain COVID-19 vaccines and their outcomes. Methods: We analysed PubMed, the Vaccine Adverse Events Reporting System (VAERS), and our database for instances of biopsy-proven LPDs following COVID-19 vaccines. Results: Fifty cases of biopsy-proven LPDs arising after COVID-19 vaccination were found: 37 from medical literature, 11 from VAERS and two from our institution. Geographical distribution revealed the most cases in the United States, Italy, and Greece, with single cases in Spain, Colombia, Canada, Japan, and Romania. The average age of patients was 53; with a slight male predominance (male-to-female ratio of 1.5:1). The Pfizer-BioNTech vaccine was associated with LPDs in 36/50 (72%) cases, aligning with its 70% share of the global vaccine market. Histopathology revealed CD30+ in 80% of cases. The most prevalent form of LPD was lymphomatoid papulosis (LyP, 30%). All reported cases produced favourable outcomes (either complete or near-complete remission). Therapeutic approaches ranged from observation to treatment with steroids, methotrexate, or excision. Conclusion: LPDs after COVID-19 vaccination appear in the context of the same vaccines (proportionally to their global market shares), share clinical and pathological findings, and have indolent, self-limited character.

Relapsing White Matter Disease and Subclinical Optic Neuropathy: From the National Multiple Sclerosis Society Case Conference Proceedings

A 16-year-old adolescent boy presented with recurrent episodes of weakness and numbness. Brain MRI demonstrated subcortical, juxtacortical, and periventricular white matter T2 hyperintensities with gadolinium enhancement. CSF was positive for oligoclonal bands that were not present in serum. Despite treatment with steroids, IV immunoglobulins, plasmapheresis, and rituximab, he continued to have episodes of weakness and numbness and new areas of T2 hyperintensity on imaging. Neuro-ophthalmologic examination revealed a subclinical optic neuropathy with predominant involvement of the papillomacular bundle. Genetic evaluation and brain biopsy led to an unexpected diagnosis.