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Introduction: PRP is a rare entity of unknown etiopathogenesis. Lack of management guidelines makes it a challenge for clinicians., Objective: To add our experience to increase evidence about PRP., Methods: We performed a retrospective, descriptive and multicentric study of 65 patients with PRP, being the largest European case series of patients with PRP., Results: PRP was more frequent in male patients with an average age of 51 years, but erythrodermic forms presented in older patients (average age 61 years). Six (75%) paediatric patients and ten (60%) non-erythrodermic adults controlled their disease with topical corticosteroids. On the contrary, 26 (68%) erythrodermic patients required biologic therapy as last and effective therapy line requiring an average of 6.5 months to achieve complete response., Conclusion: Our study showed a statistical difference in terms of outcome and response to treatment between children or patients with limited disease and patients who develop erythroderma., (Copyright © 2024 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

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., (© 2023 Australasian College of Dermatologists.)

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.

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., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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.

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 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.

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 10 9 /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.

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.

Crizotinib is a multi-target receptor tyrosine kinase inhibitor which is of great importance for the management of ALK-rearranged non-small cell lung cancer (NSCLC) patients. Serious erythroderma and toxic epidermal necrolysis have been reported associated with crizotinib treatment. The underlying mechanisms have not been examined. In this study, we tested the toxicity of crizotinib on immortal human keratinocytes (HaCaT) and human primary keratinocytes. We found that crizotinib directly cause cytotoxic on these two cells, which could be the explanation of the clinical characteristic of pathology. Apoptosis was observed and Z-VAD-FMK, a pan-caspase inhibitor can almost totally reverse the apoptosis induction effect of crizotinib. However, mitochondrial dysfunction and DNA damage were not involved in crizotinib-induced apoptosis, indicating the intrinsic apoptosis pathway have no connection with this cutaneous toxicity. Further studies showed that crizotinib significantly increased cleaved-caspase-8, a signaling protein of extrinsic apoptosis pathway, in a concentration and time-dependent manner. Moreover, we found the targets of crizotinib were not involved in HaCaT cells apoptosis. Collectively, our findings first report keratinocytes apoptosis is the key cause of crizotinib-induced cutaneous toxicity. We also reveal crizotinib induce apoptosis through the extrinsic apoptosis pathway due to detected up-regulated cleaved-caspase-8. Meanwhile, the apoptosis is independent of mitochondrial dysfunction, DNA damage and related drug targets inhibition., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A Rock Alpine doe ( Capra aegagrus hircus ) was presented to the Colorado State University Veterinary Teaching Hospital because of scaling and ulceration over the withers, coronary bands, and dewclaws. The doe was euthanized because of poor prognosis associated with a radiographically identified cranial mediastinal mass, increased respiratory effort, and discomfort. Autopsy revealed a cranial mediastinal mass, and scaling-to-ulcerative lesions affecting the dorsum, ventrum, pinna, neck, teats, coronary bands, and dewclaws. Histologically, the mediastinal mass was an epithelial neoplasm with admixed non-neoplastic T lymphocytes, consistent with a lymphoepithelial (mixed) thymoma. Sections of affected skin were characterized by hyperkeratotic cell-rich interface dermatitis with transepidermal and follicular apoptosis. Thymoma-associated exfoliative dermatitis has been recognized in cats and a rabbit, but has not been reported previously in a goat, to our knowledge. Given that thymomas are not uncommon in goats, thymoma-associated exfoliative dermatitis should be considered a clinical differential in goats with dermatologic disease.

Crusted scabies is a rare and extreme manifestation of scabies that is observed mainly among immunosuppressed patients. We describe the case of a 55-year-old patient with a history of HIV infection and injection drug use. The patient was not on any antiretroviral therapy during the previous year, was malnourished and was living in unsanitary conditions. He had extensive, generalized, thick, hyperkeratotic, crusting, papular lesions, which had evolved over the previous month. Hyperkeratotic areas were fissured and linear excoriations were noted diffusely. The rash was distributed on the entire body from the scalp to the toes, with mild itching. Microscopic examination of the scale revealed numerous scabies mites and eggs. The patient was treated with topical scabicidal agents, which resulted in complete resolution. Because of the extremely contagious nature of crusted scabies, as well as its potential for complete cure with an appropriate therapy, there should be a high degree of suspicion for this disease in patients with AIDS, even when the lesions do not have the classical appearance. Nosocomial transmission of scabies from patients with AIDS is a risk, and protective measures, early diagnosis, and therapy are essential.

The present authors have previously reported that chronic idiopathic erythroderma (CIE) that lasts for more than 3 months without specific causes occurs almost exclusively in older men. No standardized therapeutic treatments for the condition have been established to date. To assess the efficacies and safeties of current treatments for CIE, the present authors reviewed cases of CIE. Twenty cases were identified, of which CIE was treated with oral corticosteroids, oral cyclosporine A (CsA), ultraviolet therapy, or a combination of these therapies. CIE was cured in 8/20 (40%) of these cases, and the average time to cure was 19.3 months. Oral CsA was the most effective treatment at relatively low doses (50-100 mg/day), which resulted in cures in four cases. Ultraviolet therapy also effectively cured two subjects, and oral corticosteroids cured one patient. In patients that were treated with oral CsA or corticosteroids, the terminations of the treatments within 2 to 3 months resulted in relapses in multiple patients. The maintaining of the treatments for a certain period may be necessary in cases that involve treatments with these orally administered drugs. Although CIE is a chronic and potentially refractory disease, it can evidently be cured or well controlled via appropriate long-term therapies., (© 2019 Wiley Periodicals, Inc.)

Severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome is a recently recognized syndrome caused by mutations in the desmoglein 1 (DSG1) and desmoplakin (DSP) genes. Only two cases of SAM-DSP have been reported. We report on a 2-year-old girl presenting with pustular lakes within areas of erythema and large accumulations of intraepidermal neutrophils, which initially led to our misdiagnosis of generalized pustular psoriasis. No mutation was found in either the IL36RN or CARD14 genes by Sanger sequencing. The distinctive manifestations of erythroderma with severe itching, hypotrichosis, enamel defects, onychodystrophy, palmoplantar keratoderma and the crucial result of de novo missense mutation in exon 14 of the DSP gene (c.1828T>C, p.S610P) discovered by next-generation sequencing finally confirmed the diagnosis of SAM syndrome. The eruptions significantly improved after a 4-week treatment with oral acitretin and topical pimecrolimus. Oral gabapentin was prescribed simultaneously for 4 months, relieving her skin pruritus and suggesting that early treatment with pimecrolimus, acitretin and gabapentin for SAM-DSP syndrome is effective. It may even inhibit multiple allergies induced by skin barrier injury. In this work we also review the clinical features, differential diagnoses and pathological manifestations of SAM-DSP syndrome., (© 2019 Japanese Dermatological Association.)

Background: Serum copper has been reported to be increased in various cancers, including lymphoma. The purpose of the present study was to investigate the clinical and prognostic importance of serum copper levels in patients with cutaneous T-cell lymphoma (CTCL)., Patients and Methods: Serum copper was measured in 60 men and 38 women with mycosis fungoides (MF) and 14 men and 3 women with erythrodermic CTCL (6 with Sézary syndrome) consecutively evaluated from July 1980 to June 1985., Results: A greater than normal copper level was present in nearly 20% of patients and was associated with an increased risk of disease progression and shortened disease-specific survival for patients with patch or plaque phase MF, but not for those with tumor phase MF or erythrodermic CTCL. In contrast, the serum lactate dehydrogenase level and neutrophil/lymphocyte ratio were not significantly associated with prognosis in our patient cohort., Conclusion: The reason for the association between the high serum copper levels and adverse prognosis is unknown. We hypothesized that interleukin-6 is secreted primarily by non-neoplastic cells at MF skin sites, leading to release of copper by the liver. Local production of interleukin-6 at the lesion sites might conceivably also promote neoplastic cell progression by stimulation of the STAT3 pathway. Further studies on the relationship between activated tumor-associated macrophages, serum copper levels, interleukin-6, or C-reactive protein and prognosis might be informative., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Erythrodermic psoriasis (EP) is the most severe form of psoriasis, resulting in significant morbidity and mortality. International guidelines on EP treatment are lacking, with most of the biologic drugs being used basing on case reports or small case series. Ixekizumab, a fully human anti-interleukin (IL)-17A monoclonal antibody, is approved for moderate to severe plaque psoriasis while its use in EP is off label. However, two studies conducted on eight Japanese EP patients have showed ixekizumab as an efficacious and well tolerated therapy up to 24 and 52 weeks, respectively. To date, no case reports on Caucasian patients have been described. We report the case of a 66-year-old Caucasian female with EP successfully treated with ixekizumab, reaching PASI 100 after only 6 weeks of therapy and still maintaining this response at week 24. Our case report suggests ixekizumab as a highly efficacious treatment in EP, presenting also a very rapid action which leads to complete resolution of the disease after 6 weeks. Further studies are warrant to confirm our data, with controlled trials specifically dedicated to EP being strictly needed in order to verify the role and efficacy of the new biologics in EP., (© 2019 Wiley Periodicals, Inc.)

Erythroderma is a dermatologic emergency with potentially serious consequences. Several diseases with different etiologies characteristically appear as erythroderma. Depending on the age groups, congenital ichthyosiform disorders, infections, preexisting dermatoses, drug eruptions, and internal malignancies commonly present with, or progress to, erythroderma. The course, prognosis, and management strategies also vary depending on the cause of erythroderma; hence, an accurate diagnosis is essential in minimizing associated morbidity and mortality. The generalized erythema and scaling often obscure the classic clinical features of the underlying skin diseases, posing a diagnostic challenge to dermatologists. Awareness and elicitation of subtle signs and clinical manifestations are crucial. A step-wise approach ensures completeness of clinical evaluation and avoids missing any relevant clinical data. The initial clinical presentation, cutaneous examination findings, and systemic clues reveal important information regarding the diagnosis, course, and prognosis of erythroderma. The age at onset, symptomatology, duration of illness, initial lesions, initial site of onset, clinical course, family history, types of scales, changes in cutaneous integuments and systemic clues will assist in delineating the nature of underlying disease., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We report herein a case of a 72-year-old man with pityriasis rubra pilaris (PRP) that was refractory to conventional therapies. His skin lesions progressed to generalized erythroderma despite anti-interleukin (IL)-17A antibody therapy. Topical corticosteroids, emollients, systemic retinoid, methotrexate, cyclosporin and phototherapy yielded no therapeutic response. However, blockade of IL-12/23 p40 dramatically improved his cutaneous lesions. Complete remission was achieved 4 weeks after the first injection of ustekinumab and maintained for more than 48 weeks. Our data indicate that IL-12 was associated with the onset of PRP in this patient, rather than IL-23. IL-12 is critical for the differentiation of T-helper (Th)1 cells. Thus, the Th1 pathway may be associated with the onset of PRP., (© 2018 Japanese Dermatological Association.)

We report the case of an 88-year-old Japanese man with erythrodermic involvement of T-cell prolymphocytic leukemia (T-PLL). He had a history of pharyngeal diffuse large B-cell lymphoma successfully treated with polychemotherapy including cyclophosphamide and epirubicin, 6 years before the current illness. He presented with numerous reddish, coalescing, flat-topped papules on the trunk and extremities, sparing the skin folds of the abdomen, the features of which mimicked those of papuloerythroderma. Immunohistochemistry showed perivascular and epidermotropic infiltration of CD3 + CD4 + T cells in the cutaneous lesion. However, flow cytometric analysis revealed that the skin infiltrating T cells were negative for surface CD4, and that CD3 + CD4 - CD8 - cells made up 92% of the T-cell fraction of peripheral blood. The circulating atypical T cells had a round or oval nucleus and prominent nucleoli, and the deletion of chromosomes 6q, 13 and 17. These cytological profiles were consistent with those of T-PLL and distinct from those of Sézary cells. The same T-cell clone was detected in the cutaneous lesion and peripheral blood, but the expression of CD62L was absent in the skin infiltrates and present in the circulating cells. No specific mutation was detected in STAT3 or STAT5B. Although low-dose oral etoposide had a beneficial effect on the skin rash, a fatal crisis of marked leukocytosis (169 × 10 3 /μL) occurred 19 months after the illness onset. CD62L-leukemic cells of T-PLL may infiltrate the skin to form papuloerythroderma-like cutaneous lesions., (© 2018 Japanese Dermatological Association.)

Pityriasis rubra pilaris (PRP) is a rare, chronic, heterogeneous, papulosquamous inflammatory dermatosis of unknown etiology. Although erythematous scaly patches characterize the classic presentation of PRP, a broad range of clinical presentations has been reported. Histologically, PRP is characterized by psoriasiform acanthosis with alternating orthokeratosis and parakeratosis and rarely small acantholytic foci. In this article, we report a patient who presented with diffuse erythroderma and extensive acantholysis mimicking pemphigus vulgaris histologically.

Background: Phosphoinositide 3-kinase (PI3K) inhibitors are a class of small-molecule inhibitors approved for the treatment of certain leukaemias and lymphomas. Their dermatological adverse event profile is poorly described., Aim: To characterize a rare cutaneous adverse event from PI3K inhibitors in order to help dermatologists and oncologists identify and effectively manage such eruptions., Methods: This was a retrospective analysis of patients receiving PI3K inhibitors referred to the Skin Toxicities Program in The Center for Cutaneous Oncology., Results: Three patients on PI3K inhibitors for treatment of malignancy developed diffuse erythroderma and keratoderma. Clinical and histopathological findings were consistent with pityriasis rubra pilaris (PRP)-like reactions. All patients improved with topical and oral corticosteroids, oral acitretin, and drug discontinuation., Conclusions: PRP-like cutaneous eruptions may develop secondary to PI3K inhibition. Early dermatological evaluation of cutaneous toxicities to PI3K inhibitors as well as rapid initiation of disease-specific treatments may help keep patients on life-prolonging anti-cancer therapies., (© 2018 British Association of Dermatologists.)

Peeling skin syndromes form a large and heterogeneous group of inherited disorders characterized by superficial detachment of the epidermal cornified cell layers, often associated with inflammatory features. Here we report on a consanguineous family featuring noninflammatory peeling of the skin exacerbated by exposure to heat and mechanical stress. Whole exome sequencing revealed a homozygous nonsense mutation in FLG2, encoding filaggrin 2, which cosegregated with the disease phenotype in the family. The mutation was found to result in decreased FLG2 RNA levels as well as almost total absence of filaggrin 2 in the patient epidermis. Filaggrin 2 was found to be expressed throughout the cornified cell layers and to colocalize with corneodesmosin that plays a crucial role in maintaining cell-cell adhesion in this region of the epidermis. The absence of filaggrin 2 in the patient skin was associated with markedly decreased corneodesmosin expression, which may contribute to the peeling phenotype displayed by the patients. Accordingly, using the dispase dissociation assay, we showed that FLG2 downregulation interferes with keratinocyte cell-cell adhesion. Of particular interest, this effect was aggravated by temperature elevation, consistent with the clinical phenotype. Restoration of corneodesmosin levels by ectopic expression rescued cell-cell adhesion. Taken together, the present data suggest that filaggrin 2 is essential for normal cell-cell adhesion in the cornified cell layers., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)