HLA-DR Helps to Differentiate Erythrodermic Cutaneous T-cell Lymphoma from Erythrodermic Inflammatory Dermatoses in Flow Cytometry.

Differential diagnosis of erythroderma is challenging in dermatology, especially in differentiating erythrodermic cutaneous T-cell lymphoma from erythrodermic inflammatory dermatoses. This study retrospectively reviewed the peripheral blood flow cytometric results of 73 patients diagnosed with erythroderma at Peking University First Hospital from 2014 to 2019. The flow cytometry antibody panel included white blood cell markers, T-cell markers, B-cell markers, T-cell activation markers, and T helper cell differentiation markers. Features of the cell surface antigens were compared between 34 patients with erythrodermic cutaneous T-cell lymphoma and 39 patients with erythrodermic inflammatory dermatoses. The percentage of HLA-DR+/CD4+T cells was the most pronounced marker to distinguish erythrodermic cutaneous T-cell lymphoma from erythrodermic inflammatory dermatoses, with a threshold of 20.85% (sensitivity 96.77%, specificity 70.37%, p = 0.000, area under the curve (AUC) 0.882), suggesting its potential capability in the differential diagnosis of erythrodermic cutaneous T-cell lymphoma from erythrodermic inflammatory dermatoses. Moreover, in contrast to erythrodermic inflammatory dermatoses, the percentage of Th17 cells was significantly downregulated in erythrodermic cutaneous T-cell lymphoma (p = 0.001), demonstrating a dysregulated immune environment in erythrodermic cutaneous T-cell lymphoma.

Rapid and successful effects of combining dupilumab with ultraviolet B radiation therapy in the treatment of Papuloerythroderma of Ofuji.

Papuloerythroderma of Ofuji (PEO) is an uncommon disease characterised by widespread erythroderma composed of intensely pruritic solid papules coalescing into plaques sparing the skin folds (deck-chair sign). The pathogenesis of PEO remains unclear, although T helper (Th) 2 and Th22 cells may play an important role. Dupilumab is an interleukin (IL)-4 receptor α-antagonist that effectively reduces Th2 responses, which has drawn increasing attention in the treatment of PEO patients. Here, we reported a successful case of dupilumab treatment in combination with ultraviolet B (UVB) radiation therapy, which is well known and effective for chronic itch. The patient had a significant decrease in visual analogue scale (VAS) score and eosinophil after only 1 week of treatment, which may be due to the combination effect.

Severe Erythroderma Due to Adult-onset Still's Disease-like Disease Related to Graft-versus-host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

A 35-year-old woman was treated with chemotherapy for leukemia. One year later, allogeneic hematopoietic stem cell transplantation (HSCT) was performed with umbilical cord blood. After nine months, she developed a spiking fever, sore throat, arthralgia, pleural effusion, hyperferritinemia, and persistent generalized pruritic erythema. A skin biopsy showed dyskeratotic cells in the epidermis, neutrophil infiltration in the epidermis and upper dermis, and neutrophils in the parakeratotic layer. Treatment with tocilizumab was effective. Adult-onset Still's disease (AOSD)-like disease related to graft versus-host disease (GVHD) after HSCT was suspected. Abnormal immune states related to GVHD may cause AOSD-like disease with more severe skin lesions than usual.

Multisystemic eosinophilic epitheliotropic disease in three donkeys.

Multisystemic eosinophilic epitheliotropic disease (MEED) is a rare condition of equids characterized by eosinophilic infiltration of multiple organs. Clinical signs are variable depending on the affected organs. The most common clinical signs include chronic weight loss, diarrhoea and exfoliative dermatitis. Respiratory distress and raised liver enzymes are less frequently seen. The cause is unknown and the pathogenesis is poorly understood. There are less than 50 reported cases of horses with MEED. We now document the lesions in three donkeys with fluctuating or chronic loss of weight, lethargy, exfoliative dermatitis and peripheral eosinophilia. All three animals were euthanized due to poor prognosis and welfare concerns. Post-mortem examination revealed multiple white to tan, irregular masses composed of eosinophilic infiltrates, including eosinophilic granulomas in several organs, confirming the presence of MEED. To the best of our knowledge, MEED has not previously been reported in donkeys.

A High Programmed Cell Death Protein 1 Hormone Receptor Score on Skin Biopsy is Associated with Sézary Syndrome Diagnosis: A Study of 91 Patients with Erythroderma.

Erythroderma is challenging to diagnose. The aim of this single-centre retrospective study was to identify factors that can be used to improve the diagnosis of erythroderma. Among 91 patients with erythroderma, 21 were diagnosed with eczema, 17 with psoriasis, 20 with drug-induced erythroderma, 13 with erythrodermic mycosis fungoides and 20 with Sézary syndrome. Nail alterations, ear involvement, and severe scaling were significantly associated with psoriasis (p = 0.044). Fever and hypereosinophilia were associated with drug-induced erythroderma. Expression of programmed cell death protein 1 was observed in all skin biopsies. However, with Sézary syndrome, programmed cell death protein 1 expression was significantly higher than with other aetiologies. A programmed cell death protein 1 hormone receptor score (H-score) >50 was associated with Sézary syndrome (p < 0.001, sensitivity 75%, specificity 92%) as well as CXCL13 expression (p < 0.044). CD7 loss was more frequent with erythrodermic mycosis fungoides and Sézary syndrome (p = 0.022). This study reports the importance of programmed cell death protein 1 expression for the differential diagnosis of Sézary syndrome and other aetiologies, including erythrodermic mycosis fungoides.

Sézary Syndrome: Different Erythroderma Morphological Features with Proposal for a Clinical Score System.

Sézary syndrome is a rare subtype of cutaneous T-cell lymphoma characterized by erythroderma, peripheral lymphadenopathies, and circulating atypical cerebriform T-cells. To date, no definite staging system has been developed for these patients. In this retrospective analysis of the archive of the Dermatological Clinic of the University of Turin, Italy, erythrodermic SS patients were classified according to clinical records and photographs into three main presentations: erythematous, infiltrated, or melanodermic. The pattern of erythroderma was found to be associated with disease outcome, as better survivals were recorded in patients with erythematous and infiltrative erythroderma. Patients in the melanodermic group, though less represented in our investigation, seemed to show a worse trend in survival. According to this preliminary evidence, a new prognostic classification, with a revised score specific for Sézary syndrome patients, can be proposed to usefully integrate the current staging system. The correlation displayed in our research will be hopefully confirmed by prospective studies with larger cohorts, with the aim of identifying significant prognostic features in this subset of cutaneous T-cell lymphoma patients.

A novel pathogenic variant in the corneodesmosin gene causing generalized inflammatory peeling skin syndrome with marked eosinophilia and trichorrhexis invaginata.

Generalized inflammatory peeling skin syndrome (PSS) is a rare autosomal recessive genodermatosis caused by loss-of-function disease-causing variants of the corneodesmosin gene (CDSN), resulting in excessive shedding of the superficial layers of the epidermis. We describe a case of generalized inflammatory PSS in an infant, presenting at day two of life with ichthyosiform erythroderma and superficial peeling of the skin. Hair microscopy showed trichorrhexis invaginata. Normal amounts of skin LEKT1, a product of SPINK5 on immunohistochemical staining excluded a diagnosis of Netherton syndrome. Genetic analysis revealed a homozygous novel complete CDSN deletion, estimated 4.6 kb in size, supporting the diagnosis of generalized inflammatory PSS.

Leonine facies: A unique presentation of T-prolymphocytic leukemia.

We report a 52-year-old man who presented with erythroderma and nodular lesions on face manifesting as "Leonine facies". He had impaired sensation over the face and was initially diagnosed to have lepromatous leprosy and was treated with antileprosy drugs. Investigations showed a total Leukocyte count of 550 X 109/l with 90% atypical lymphoid cells with prominent central nucleolus suggestive of prolymphocytes. On flow cytometry, these cells were positive for cytoplasmic CD3, CD2, CD5, CD7, CD4, and CD38 (dim) and were negative for CD1a and TdT and diagnosis of T-prolymphocytic leukemia was made.

From SARS-CoV-2 hematogenous spreading to endothelial dysfunction: clinical-histopathological study of cutaneous signs of COVID-19.

BACKGROUND: To date, very few studies on clinical-histopathological correlations of cutaneous disorders associated with COVID-19 have been conducted. CASE PRESENTATION: The Case 1 was a 90-year-old man, who tested positive for SARS-CoV-2 from a nasopharyngeal swab. Two days later, he was hospitalized and after eleven days transferred to Intensive Care Unit. A chest CT showed bilateral ground-glass opacities. Just that day, an erythematous maculo-papular rash appeared on trunk, shoulders and neck, becoming purpuric after few days. Histological evaluations revealed a chronic superficial dermatitis with purpuric aspects. The superficial and papillary dermis appeared edematous, with a perivascular lympho-granulocytic infiltrate and erythrocytic extravasation. At intraepithelial level, spongiosis and a granulocyte infiltrate were detected. Arterioles, capillaries and post-capillary venules showed endothelial swelling and appeared ectatic. The patient was treated with hydroxychloroquine, azithromycin, lopinavir-ritonavir and tocilizumab. Regrettably, due to severe lung impairment, he died. The Case 2 was a 85-year-old man, admitted to Intensive Care Unit, where he was intubated. He had tested positive for SARS-CoV-2 from a nasopharyngeal swab two days before. A chest RX showed bilateral atypical pneumonia. After seven days, a cutaneous reddening involving trunk, upper limbs, neck and face developed, configuring a sub-erythroderma. Histological evaluations displayed edema in the papillary and superficial reticular dermis, and a perivascular lymphocytic infiltrate in the superficial dermis. The patient was treated with hydroxychloroquine, azithromycin, lopinavir-ritonavir and tocilizumab. Sub-erythroderma as well as respiratory symptoms gradually improved until healing. CONCLUSIONS: The endothelial swelling detected in the Case 1 could be a morphological expression of SARS-CoV-2-induced endothelial dysfunction. We hypothesize that cutaneous damage could be initiated by endothelial dysfunction, caused by SARS-CoV-2 infection of endothelial cells or induced by immune system activation. The disruption of endothelial integrity could enhance microvascular permeability, extravasation of inflammatory cells and cytokines, with cutaneous injury. The Case 2 developed a sub-erythroderma associated with COVID-19, and a non-specific chronic dermatitis was detected at histological level. We speculate that a purpuric rash could represent the cutaneous sign of a more severe coagulopathy, as highlighted histologically by vascular abnormalities, while a sub-erythroderma could be expression of viral hematogenous spreading, inducing a non-specific chronic dermatitis.

Interstitial granuloma after interferon-gamma and narrowband UVB therapy in a patient with mycosis fungoides: Immunological and histopathological considerations.

In mycosis fungoides (MF), cutaneous granuloma formation is unusual. Furthermore, MF showing interstitial granuloma, a rare type, after combination therapy with interferon-gamma (IFN-γ) and narrowband UVB (nbUVB) has not been previously reported. A 77-year-old man was referred to our hospital with a 2-month history of erythroderma. Biopsied specimens revealed infiltration of atypical lymphocytes and eosinophils. A diagnosis of an erythrodermic variant of MF was made. He was treated with combination therapy of IFN-γ and nbUVB. After the therapy, papules newly appeared and a histopathological specimen revealed interstitial granuloma. There were several CXCR3-positive cells around the granuloma. We speculated that the combination therapy made T-helper 1 cells migrate to the cutaneous lesion and resulted in the granuloma formation. Furthermore, judging from the disappearance of elastic fibers around the interstitial granuloma, we considered that IFN-γ may induce the infiltration of histiocytes interstitially after damage of elastic fibers caused by nbUVB therapy, and both IFN-γ and nbUVB may thus play an important role in the histogenesis. Not only histopathology but also immunological observations are needed to elucidate the mechanisms underlying the development of different types of granuloma in MF.

Eritrodermia y Linfomas Cutáneo de Células T / Erythroderma and Cutanous T - Cell Lymphoma

La eritrodermia es una erupción eritematosa más o menos escamosa que afecta a más del 90 por ciento de la superficie corporal. Se trata de una enfermedad capaz de comprometer el pronóstico vital y que puede complicarse con desequilibrios hidroelectrolíticos, trastornos de la termorregulación, infecciones, así como con fallo cardiovascular. En la presente publicación referimos el caso de un paciente masculino de 72 años con antecedentes de hipertensión arterial y de Lepra que recibió poliquimioterapia, es ingresado en el servicio de dermatología en el período de observación, pues hace alrededor de un año comenzó a presentar enrojecimiento de la piel y múltiples escamas. Al momento del examen se observa paciente eritrodérmico, ectropión, distrofia ungueal importante, con adenopatías palpables axilares e inguinales, asociado a un prurito intenso generalizado. Se realizan estudios para el diagnóstico incluyendo biopsia de ganglios inguinal y de piel, esta última compatible con Micosis Fungoide. Actualmente se reconocen tres variantes eritrodérmicas en el linfoma cutáneo de células T: el síndrome de Sézary, la Eritrodermia en micosis fungoide y la Eritrodermia en linfomas cutáneos de células T: No Especificada. Si bien se entiende al síndrome de Sézary como una expresión leucémica del linfoma cutáneo de células T eritrodérmico, con numerosas células de Sézary en piel, sangre y otros tejidos, la Eritrodermia en micosis fungoide se determinaría ante la ausencia de estos mismos hallazgos hematológicos e histológico ante un cuadro clínico eritrodérmico. Se hace necesaria la publicación del artículo por la forma de presentación de la micosis fungoide, teniendo en cuenta que esta dermatosis tiene un sin número de diagnósticos diferenciales que la hace la gran simuladora en la Dermatología(AU)

Erythroderma is a more or less scaly erythematous rash that affects more than 90 percent of the body surface area. It is a disease capable of compromising the vital prognosis and that can be complicated by hydroelectrolytic imbalances, thermoregulation disorders, infections, as well as cardiovascular failure. In this publication we refer to the case of a 72-year-old male patient with a history of high blood pressure and leprosy who received polychemotherapy, is admitted to the dermatology service in the observation period, as about a year ago he began to develop redness of the skin and multiple scales. At the time of the examination, an erythrothermal patient, ectropion, important ungueal dystrophy, with axillary and inguinal palpable adenopathies, associated with a widespread intense itching, is observed. Studies are conducted for diagnosis including inguinal and skin node biopsy, the latter compatible with Mycosis Fungoide. Three erythrodermal variants are currently recognized in skin T-cell lymphoma: Sézary syndrome, Erythroderma in fungoid mycosis, and Erythroderma in skin T-cell lymphomas: Undepede. While Sézary syndrome is understood as a leukemia expression of erythrodermal T-cell skin lymphoma, with numerous Sézary cells in skin, blood and other tissues, Erythroderma in fungoid mycosis would be determined in the absence of these same haematological and histological findings before an erythrodermal clinical picture. It is necessary to publish the article by the form of presentation of fungoid mycosis, taking into account that this dermatosis has a number of differential diagnoses that makes it the great simulator in Dermatology(EU)

Erythroderma: a prospective study of 309 patients followed for 12 years in a tertiary center.

Erythroderma is characterized by erythema and scaling affecting more than 80% of the body surface area. It is potentially life-threatening, and diagnosis of the underlying disease is a challenge. Despite laboratory improvements, many cases remain idiopathic. We aimed to analyze clinical and laboratory findings of 309 erythrodermic patients to find clues to the etiologic diagnosis. We performed a prospective study at the University of São Paulo Medical School, from 2007 to 2018, with patients with acquired erythroderma. Clinical, laboratory, histology, and molecular biology data were collected. The median age at diagnosis was 57 years, with a male-to-female ratio of 2.2. Eczema was the most frequent etiology (20.7%), followed by psoriasis (16.8%), Sézary syndrome (12.3%), drug eruption (12.3%), atopic dermatitis (8.7%), and mycosis fungoides (5.5%). Other diagnoses (6.8%) included pemphigus foliaceous, paraneoplastic erythroderma, adult T-cell leukemia/lymphoma, dermatomyositis, pityriasis rubra pilaris, lichen planus, bullous pemphigoid, and leprosy. In 52 patients (16.8%), it was not possible to elucidate erythroderma etiology. Atopic dermatitis developed erythroderma at an earlier age (median 25 years; P = 0.0001). Acute onset was associated with drug reactions and atopic dermatitis (median time from erythroderma to diagnosis of 1 and 1.5 months, respectively; P = 0.0001). Higher immunoglobulin E levels were observed in atopic dermatitis (median 24,600 U/L; P = 0.0001). Histopathology was helpful and was consistent with the final diagnosis in 72.4%. Monoclonal T-cell proliferation in the skin was observed in mycosis fungoides (33.3%) and Sézary syndrome (90.9%). At the last assessment, 211 patients (69.3%) were alive with disease, 65 (21.7%) were alive without disease, and 27 (9.1%) died with active disease. Erythroderma is a challenging syndrome with a difficult diagnostic approach. Younger age and higher immunoglobulin E levels are associated with atopic dermatitis; acute onset is observed in drug eruptions and atopic dermatitis. Histopathology and molecular biology tests are essential tools in the investigation of erythroderma.

Erythroderma as first manifestation of squamous cell lung cancer: rare case report

Abstract Erythroderma as the first manifestation of a solid organ malignancy is rare. The underlying cancer is a challenging condition to diagnose. There are a few cases of erythroderma in cancer patients reported in the literature. We here describe the case of a 70-year-old man who presented with asthenia, weight loss, dry cough and total body erythema with desquamation over the past month. A chest computed tomography scan showed a nodular lesion, which was finally diagnosed as a squamous cell lung carcinoma. To our knowledge, as an erythroderma presentation, only 13 cases have been reported in the literature. This case report demonstrates the need to search for a neoplasm in patients presenting with erythroderma, particularly in the presence of accompanying debilitating symptoms.

Familial "benign" pemphigus? Erythroderma and fatal outcome

Abstract Hailey-Hailey disease, or familial benign pemphigus, is a rare bullous genodermatosis that usually presents with flaccid blisters, erosions, and maceration limited to flexural areas, resulting in increased morbidity and reduced quality of life for affected patients. The authors report an unusual case of generalized Hailey-Hailey disease with erythroderma and fatal outcome.

[Ichtyosiform erythroderma revealing a severe combined immunodeficiency]. / Érythrodermie ichtyosiforme révélant un déficit immunitaire combiné sévère.

BACKGROUND: Severe combined immunodeficiency (SCID) is a the most severe form of primary immunodeficiency and is highly heterogeneous. We report an atypical form of SCID revealed by exfoliative erythroderma. PATIENTS AND METHODS: A 3-month-old boy, born to consanguineous parents, was admitted to the dermatology department with exfoliative erythroderma associated with eczematous patches and alopecia of the scalp, eyelashes, and eyebrows, but with no lymphadenopathy or hepatosplenomegaly. He displayed chronic diarrhea and recurrent infection since birth. A complete blood count showed marked leukocytosis with eosinophilia and lymphocytosis. These clinical and biological findings improved partly with topical steroids. The patient no longer had erythroderma and showed regrowth of hair, eyelashes and eyebrows. The subsequent CBC showed less marked eosinophilia with mild lymphopenia and no leukocytosis. Immunoglobulin levels were undetectable. Primary immunodeficiency was discussed. Immunological investigations concluded on a diagnosis of T-B-NK+ SCID. Mutation analysis revealed a homozygous c.1338C>G (pCys446Trp) mutation in the RAG2 gene. Hematopoietic stem cell transplantation is planned in the near future. CONCLUSION: This case illustrates atypical T-B-NK+ SCID revealed by severe exfoliative erythroderma in a 3-month-old boy with RAG2 gene mutation. Neonatal erythroderma must be considered a warning sign of primary immunodeficiency requiring immediate immunological phenotyping as well as genetic testing for a definitive diagnosis.