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Sézary syndrome (SS) is a rare and aggressive type of cutaneous T-cell lymphoma, with an abnormal inflammatory response in affected skin. The cytokines IL-1B and IL-18, as key signaling molecules in the immune system, are produced in an inactive form and cleave to the active form by inflammasomes. In this study, we assessed the skin, serum, peripheral mononuclear blood cell (PBMC) and lymph-node samples of SS patients and control groups (healthy donors (HDs) and idiopathic erythroderma (IE) nodes) to investigate the inflammatory markers IL-1B and IL-18 at the protein and transcript expression levels, as potential markers of inflammasome activation. Our findings showed increased IL-1B and decreased IL-18 protein expression in the epidermis of SS patients; however, in the dermis layer, we detected increased IL-18 protein expression. In the lymph nodes of SS patients at advanced stages of the disease (N2/N3), we also detected an enhancement of IL-18 and a downregulation of IL-1B at the protein level. Moreover, the transcriptomic analysis of the SS and IE nodes confirmed the decreased expression of IL1B and NLRP3 , whereas the pathway analysis indicated a further downregulation of IL1B -associated genes. Overall, the present findings showed compartmentalized expressions of IL-1B and IL-18 and provided the first evidence of their imbalance in patients with Sézary syndrome.

Erythroderma (exfoliative dermatitis) is associated with important metabolic changes that include an enhancement in energy expenditure. The key components to total energy expenditure (TEE) include basal metabolic rate (~68% of TEE), physical activity (~22% of TEE) and thermic effect of food (~10% of TEE). In the erythrodermic state, there are likely multiple contributors to the increase in basal metabolic rate, such as 'caloric drain' resulting from increased evaporation of water from enhanced transepidermal water loss, increased activity of the cardiovascular system (including high-output cardiac failure), increased nonshivering thermogenesis and hormonal changes such as hypercortisolaemia. A change in the patient's level of physical activity and appetite as a result of ill health status may further impact on their TEE and energy consumption. In Part 2 of this two-part concise review, we explore the key constituents of energy homeostasis and the potential mechanisms influencing energy homeostasis in erythroderma, and suggest much-needed dietetic management strategies for this important condition., (© 2021 British Association of Dermatologists.)

Atopic dermatitis is a chronic form of allergic contact dermatitis that is closely associated with a compromised epidermal barrier. Immunogenicity of a given electrophilic hapten after penetration of this barrier depends directly on biochemical reactions in the thiol-rich layer in the stratum granulosum. In response to electrophilic hapten, NF-erythroid 2-related factor 2 (NRF2) in keratinocytes efficiently induces the production of antioxidants. In this study, we show that the immunogenicity of a given hapten depends directly on the extent to which it induces antioxidant host defenses within the epidermal tissue. We found that allergic contact dermatitis did not develop in NRF2-deficient mice because of compromise of the epidermal innate immune responses that upregulate IL-1α. We also analyzed epidermal NRF2 in association with congenital disorders with features similar to atopic dermatitis in humans. Epidermal samples from patients with Netherton syndrome and peeling skin syndrome exhibited elevated levels of NRF2 and also elevated levels of its downstream target, small proline-rich protein 2. Taken together, these results suggest that the thiol-mediated biochemical responses in the stratum granulosum provide a critical link between defective epidermal barrier function and the development of atopy. Likewise, our results suggested that NRF2 may have a profound impact on the generation of cutaneous immunological memory., (Copyright © 2020 by The American Association of Immunologists, Inc.)

Background: Erythroderma is a severe manifestation of pemphigus foliaceus (PF), a blistering disease mediated by IgG autoantibodies against desmoglein 1. Increasing evidence supports the contribution of angiogenic mediators in the pathogenesis of erythroderma., Objective: To evaluate the in situ expression of vascular endothelial growth factor (VEGF) and endoglin in patients with PF with erythroderma., Methods: Formalin-fixed paraffin-embedded skin samples obtained from patients with erythrodermic PF (n = 19; 12 patients with endemic PF), non-erythrodermic PF (n = 17), pemphigus vulgaris (PV; n = 10), psoriasis (n = 10) and healthy individuals (HI; n = 10) were processed in an automated immunohistochemistry platform utilizing anti-VEGF and anti-endoglin as primary antibodies. Reactivity was evaluated both manually (0 = negative; 1+ = mild; 2+ = intense) and through an automated microvessel analysis algorithm., Results: Vascular endothelial growth factor expression in erythrodermic PF was higher than in non-erythrodermic PF (P = 0.034) and in HI (P = 0.004), and similar to psoriasis (P = 0.667) and PV (P = 0.667). In non-erythrodermic PF, VEGF positivity was similar to HI (P = 0.247), and lower than psoriasis (P = 0.049) and PV (P = 0.049). Both erythrodermic and non-erythrodermic PF presented similar endoglin expression (P = 0.700). In addition, endoglin positivity during erythrodermic PF was similar to psoriasis (P = 0.133) and lower than PV (P = 0.0009). Increased expression of in situVEGF suggests that healing processes are triggered in response to tissue damage led by autoantibodies in PF, especially during erythroderma. Reduced endoglin positivity suggests that an unbalanced angiogenesis may occur during erythrodermic PF. Further studies may help to confirm if the regulation of VEGF and endoglin expression in patients with PF can contribute to control the healing process and enable disease remission., Conclusion: Overexpression of VEGF in erythrodermic PF as well as in PV and psoriasis points out a dysregulated repair process in severe forms of these diseases and suggests VEGF and endoglin could act as prognostic markers and future therapeutic targets to enable proper healing in PF., (© 2018 European Academy of Dermatology and Venereology.)

Background: The histopathologic differentiation between Sézary syndrome (SS) and erythrodermic dermatitis may be extremely difficult. In this immunohistochemical study, it was investigated if thymocyte selection-associated high mobility group box protein (TOX) and C-MYC can be used as additional diagnostic markers to differentiate between SS and erythrodermic dermatitis., Method: Paraffin-embedded skin biopsies from 15 SS patients and 17 erythrodermic dermatitis patients were stained and scored for TOX or C-MYC expression., Results: Strong nuclear staining for TOX in more than 50% of skin-infiltrating T cells was observed in 13 of 15 (87%) SS cases, whereas erythrodermic dermatitis cases showed weak nuclear staining in 11-50% (median: 25%) of the T cells; strong nuclear staining as found in SS was never observed in erythrodermic dermatitis. No significant differences in C-MYC expression between SS and erythrodermic dermatitis were found. In most patients of both groups, percentages of C-MYC positive-cells varied between less than 10 and 25% of skin-infiltrating T cells., Conclusion: Our results suggest that strong expression of TOX in more than 50% of skin-infiltrating T cells in erythrodermic skin is a useful marker in the differentiation between SS and erythrodermic dermatitis, whereas staining for C-MYC does not contribute to differential diagnosis., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The clinical differential diagnosis of erythroderma is extensive and includes both benign and malignant causes. The authors present an exceptional case of erythroderma secondary to pre-B-cell lymphoblastic leukemia cutis, with diagnostic findings on biopsy.

Background: Peeling skin syndrome (PSS) is a rare autosomal recessive form of ichthyosis showing skin exfoliation. PSS is divided into acral and generalized PSS, and the latter is further classified into non-inflammatory type (PSS type A) and inflammatory type (PSS type B). PSS type B is now called peeling skin disease (PSD). Different loss-of-function mutations in the corneodesmosin (CDSN) gene have been reported to cause PSD., Objective: The aim of this study was to determine genetic basis of disease in a 14-year-old Japanese patient with PSD., Methods and Results: Immunohistochemical study showed lack of corneodesmosin (CDSN) in the skin, and standard PCR for genomic DNA failed to amplify CDSN product, suggesting CDSN defect. Multiplex ligation-dependent probe amplification and genomic quantitative real-time PCR analyses detected large homozygous deletion of 59,184bp extending from 40.6kb upstream to 13.2kb downstream of CDSN, which included 6 genes (TCF19, CCHCR1, PSORS1C2, PSORS1C1, CDSN and C6orf15). The continuous gene lost did not result in additional clinical features. Inverted repeats with 85% similarity flanking the deletion breakpoint were considered to mediate the deletion by non-homologous end joining or fork stalling and template switching/microhomology-mediated break-induced replication. Parents were clinically unaffected and were heterozygote carriers of the same deletion, which was absent in 284 ethnically matched control alleles. We also developed simple PCR method, which is useful for detection of this deletion., Conclusion: Although 5 other genes were also deleted, homozygous deletion of CDSN was considered to be responsible for this PSD., (Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Atopic dermatitis (AD), Netherton syndrome (NS) and peeling skin syndrome type B (PSS) may show some clinical phenotypic overlap. Corneodesmosomes are crucial for maintaining stratum corneum integrity and the components' localization can be visualized by immunostaining tape-stripped corneocytes. In normal skin, they are detected at the cell periphery., Objective: To determine whether AD, NS, PSS and ichthyosis vulgaris (IV) have differences in the corneodesmosomal components' distribution and corneocytes surface areas., Methods: Corneocytes were tape-stripped from a control group (n=12) and a disease group (37 AD cases, 3 IV cases, 4 NS cases, and 3 PSS cases), and analyzed with immunofluorescent microscopy. The distribution patterns of corneodesmosomal components: desmoglein 1, corneodesmosin, and desmocollin 1 were classified into four types: peripheral, sparse diffuse, dense diffuse and partial diffuse. Corneocyte surface areas were also measured., Results: The corneodesmosome staining patterns were abnormal in the disease group. Other than in the 3 PSS cases, all three components showed similar patterns in each category. In lesional AD skin, the dense diffuse pattern was prominent. A high rate of the partial diffuse pattern, loss of linear cell-cell contacts, and irregular stripping manners were unique to NS. Only in PSS was corneodesmosin staining virtually absent. The corneocyte surface areas correlated significantly with the rate of combined sparse and dense diffuse patterns of desmoglein 1., Conclusion: This method may be used to assess abnormally differentiated corneocytes in AD and other diseases tested. In PSS samples, tape stripping analysis may serve as a non-invasive diagnostic test., (Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Pemphigus foliaceus (PF) represents an autoimmune blistering disease characterized by the disruption of epidermal intercellular adhesion proteins. Clinical findings include superficial crusted erosions in a seborrheic distribution; however, the disease can rarely present as an exfoliative erythroderma. Histopathologic findings include acantholysis with cleavage within the granular layer. Direct immunofluorescence studies show intercellular IgG and complement deposition. We present two patients, to our dermatology department, with a previous diagnosis of psoriasis, with an exfoliative erythroderma, which ultimately proved to be because of PF based on histopathological features, direct immunofluorescence results and levels of antibodies against desmoglein 1. Both patients responded well to oral prednisone and rituximab. This variant of PF should be entertained in both the clinical differential diagnosis of psoriasiform erythroderma and in the microscopic differential diagnosis of psoriasiform epidermal hyperplasia with focal acantholysis, particularly in patients for whom the clinical history is not classic for psoriasis or for whom conventional psoriasis therapies have not proven beneficial., (Copyright © 2012 John Wiley & Sons A/S.)

Background: Stratum corneum (SC) readily dislodgeable exfoliation could affect percutaneous absorption and thus influence treatment and toxicological effects. Urea, a classical enhancer, is absorbed less than 1% in vivo in man and might be a useful marker to quantify chemical-drug exfoliation. This study develops a simple model utilizing washing and tape-stripping to quantify surface loss of chemicals topically applied on human skin and estimate the extent of chemical-drug SC exfoliation., Methods: Urea, 10% as a model hydrophilic chemical marker, was applied to human skin on identical sites (5 cm(2)/area with 1.8 mg/cm(2) urea) in vitro and in vivo. At time points 0, 4, and 6 h, the area was washed, rubbed, and stripped five times with cellophane tape. Quantitative urea was performed by colorimetric assay., Results: The data of the in vitro protected non-exfoliating model, as the control, showed no statistical difference between 0-, 4-, and 6-h recovery (P > 0.05). In the air-exposed model in vivo exfoliation in man, the recovery decreased from 98.8 ± 3.7% to 93.9 ± 6.8% in 4 h and 86.4 ± 3.0% in 6 h (P = 0.02). In the cloth-covered model in vivo, the recovery decreased from 99.4 ± 5.8% to 84.9 ± 5.3% in 4 h (P = 0.04), which reached 73 ± 2.8% within 6 h (P = 0.007)., Conclusions: This study suggests that urea, measured with washing, rubbing, and tape-stripping, can be used as a possible chemical-drug SC readily dislodgeable exfoliation and friction rubbing metric. In addition, this might help to determine the rule of skin exfoliation in dermatopharmacologic and dermatoxicologic assessment.

Erythroderma may be secondary to a cutaneous T-cell lymphoma (CTCL) and various other erythrodermic inflammatory dermatoses (EID), and their histopathologic distinction is often difficult. The aim of this study was to determine if morphological parameters, namely: the presence of b-catenin, and JunB (previously shown to be expressed by CTCL cells), the epidermal CD8:CD3 ratio, and CD30 expression may help in the histopathologic diagnosis of erythroderma, especially in differentiating CTCL and EID. We retrospectively reviewed a series of 47 skin biopsies from patients with erythroderma (18 CTCL and 29 EID). The diagnosis of each case was established using clinical, biological and histopathologic data. After a blind assessment of the hematoxylin--eosin--safran stained slides, a correct diagnosis of the underlying cause of erythroderma was made only in 31% of cases. A correct differential diagnosis between lymphoma and EID was done with certainty in 57% of cases. Various morphologic and phenotypic parameters were then recorded and we compared their frequency in the CTCL versus the EID group. With the exception of atypical lymphocytes, the moderate to high density of dermal infiltrates and Pautrier microabcesses, only found in CTCL, no morphologic parameter was found to be specific of CTCL, although single lymphocytes epidermotropism, telangiectasias, and slight lymphocytic dermal infiltrate were significantly more frequent in EID. A low (<10%) CD8:CD3 ratio in the epidermal lymphocytic infiltrate and dermal CD30+ lymphocytes were significantly more frequent in CTCL. JunB expression by lymphocytes was specific of CTCL, but was inconstant in our series (17%). We found β-catenin expression in a minority of cases from both the CTCL and EID groups. Among EID, dermal suprapapillary thinning was specific of psoriasis. Neutrophils exocytosis and edema of papillary dermis were significantly more frequent in psoriasis, and spongiosis was more frequent in eczema. In conclusion, few morphological and phenotypical parameters are helpful in making a differential diagnosis between erythrodermic CTCL and EID using paraffin embedded skin biopsies.

Background: Erythrodermas are often life-threatening conditions in infants. Determination of the underlying cause is crucial. Microscopic changes in adult erythroderma lack specificity., Objective: To determine if an early skin biopsy is helpful for the diagnosis of neonatal and infantile erythroderma., Methods: Seventy-two patients admitted for erythroderma in the first year of life were retrospectively included. One hundred and eleven skin biopsies (12-year period) were examined by 3 pathologists blinded to the clinical diagnosis, and classified into atopic dermatitis, immunodeficiency (ID), psoriasis, Netherton syndrome (NS), ichthyosis, other. From year 2000, LEKTI antibody was performed when NS was suspected. Pathological diagnosis was then compared with clinical diagnosis., Results: The final diagnosis was made in 69.3% of the cases. In 57.6%, pathological diagnosis was in accordance, and in 11.7%, it was in accordance, but other diagnosis had also been proposed. For ID, sensitivity and specificity were 58.5 and 98.5%, respectively. Before year 2000, NS was frequently misdiagnosed with psoriasis, but with the use of LEKTI antibody, sensitivity and specificity were 100%., Conclusion: Skin biopsy is helpful for etiologic diagnosis of early erythroderma of infancy, particularly in ID and NS, the most severe diseases. Consequently, these results justify an early systematic skin biopsy for a better and earlier management.

Background: Psoriasis is a chronic inflammatory cutaneous disorder. It is marked by aberrant epidermal and dermal expression of cytokines., Aim: Evaluate the expression of proinflammatory cytokines in a particular severe form of psoriasis the psoriatic erythroderma., Methods: We focused on intra-lesional cytokine gene expression in cutaneous biopsies of lesional site and their correspondent non lesional skin. On the whole, four healthy volunteers and thirty six patients were included in this study. Among these, three had a psoriatic erythroderma. Assuming that local production of cytokines may be approached by mRNA cytokine quantification, the expression of alpha tumour necrosis factor (TNFalpha) and interleukin-8 (IL-8) was analyzed by reverse transcription and real time quantitative polymerase chain reaction., Results: Under expression of all selected molecules in psoriatic erythroderma lesions was contrasted with the data obtained in the other psoriatic lesion forms witch revealed that ratios had significantly increased in lesional skin compared with non lesional one. However, at anatomy-pathology analysis, inflammatory infiltrate in psoriatic erythroderma was classical poor and no specific of this disease, such as the case of our three patients. This could explain the drop of intra-lesional inflammatory mediators., Conclusion: The paradoxal low levels of proinflammatory cytokines in psoriatic erythroderma are an original and important result.

Erythroderma in neonates and infants is a frequently encountered problem in the daily practice of pediatric dermatology. The objective of this study was to determine the frequency of various causes of this clinical entity, as well as which clinical and laboratory findings are useful in the differentiation of these causes, and to assess the evolution of this disease in this age group. Forty-two patients with erythroderma under 1 year of age were included in this study. A follow-up period of 3-5 years was completed. The study was performed in the Department of Dermatology, Al-Sadr and Alhakeem teaching hospitals and a private section in Najaf governorate, Iraq during the period 1998-2006. The diagnosis was made at an average of 3 months after the onset of the disease. The underlying causes included seborrheic dermatitis in 21.4%, atopic dermatitis in 14.3%, different types of Ichthyoses in 31.5%, psoriasis in 4.7%, pityriasis rubra pilaris in 2.4%, Staphylococcal scalded skin syndrome in 7.14%, Netherton syndrome in 4.7%, immune deficiency syndromes in 4.8% and undetermined erythroderma in 9.5% of the patients. Of 29 cases, histopathological examination of skin biopsy showed non-specific features in 58.7% and could confirm the diagnosis in 41.3% cases. The prognosis was poor with a mortality rate of 26.2% and severe dermatoses persisted in 60% of the survivors. It is difficult to make the etiological diagnosis of neonatal erythroderma from the first examination. Associated immune deficiency should be suspected if the condition associated with skin indurations, severe alopecia, failure to thrive and/or have infectious complications. The prognosis is poor especially in those with immune deficiency or a chronic persistent course.

Erythrodermic cutaneous T-cell lymphoma (E-CTCL) is the cause of less than 5% of all cases of generalized erythroderma. A methodical evaluation of skin, blood, and lymph node samples using standard histology, immunohistochemistry (IHC), flow cytometry (FC), and molecular analysis for evidence of a dominant T-cell clone has been recommended in a recently published diagnostic algorithm. In this commentary, the author discusses available information regarding the role of these diagnostic methods for the diagnosis of E-CTCL with emphasis on personal observations regarding skin IHC and polymerase chain reaction (PCR)-based molecular studies as adjunct diagnostic studies on a series of 55 patients with erythrodermic mycosis fungoides and 50 patients with Sézary syndrome compared to 50 patients with extensive benign inflammatory skin disease. The conclusions are (1) IHC of the skin does not reliably differentiate E-CTCL from benign simulants, (2) presence of phenotypically abnormal T cells in the blood or expanded subsets of CD4+CD7- or CD4+CD26- cells by FC is particularly helpful as a diagnostic study, (3) the presence of an identical T-cell clone in the skin and blood also is a specific diagnostic criterion for E-CTCL, but exceptions may occur, and (4) the PCRgamma-denaturing gradient gel electrophoresis technique appears to be more reliable than PCRgamma-single-stranded conformational polymorphism for diagnostic purposes.

The increasing use of new drugs in cancer therapy, especially growth factors, hormones, and chemotherapies resulted in several reports of unusual skin eruptions. We studied a patient with erythroderma who had received erythropoietin because of myeloma with tumor anemia. The histological features were characterized by a lichenoid, focally granulomatous infiltrate with predominance of histiocytes. It is important for dermatopathologists to recognize this interesting pattern induced by erythropoietin.

Objective: To report a case of elevated blood tacrolimus concentration after application of topical tacrolimus ointment in an erythrodermic patient., Case Summary: A 44-year-old man developed generalized erythroderma and itching due to infection with human T-cell lymphotropic virus. Despite application of strong glucocorticosteroid ointments, the symptoms and area of erythroderma were not alleviated. Daily topical application of tacrolimus 0.1% ointment was added and therapeutic drug monitoring was started. The dose and applied area of tacrolimus were gradually increased from 2.5 to 12.5 g/d and from 10% to 90% of body surface area, respectively. Because the trough concentration of tacrolimus in whole blood increased from 7.5 ng/mL on treatment day 9 to 15.4 ng/mL on day 13, the dose was reduced to 10 g/d. However, the concentration further elevated to 16.5 ng/mL. Therefore, the applied area was reduced to 20% of body surface area, and the tacrolimus concentration decreased gradually thereafter. Although the transient increase of blood tacrolimus concentration was observed on day 23, treatment with 20% applied area and 5 g/d were maintained., Discussion: Topically applied tacrolimus was substantially absorbed with the expansion of its applied area and dose. Increased tacrolimus concentrations may have a tendency to depend on the increase of the percent of body surface area per dose. Our findings showing the elevation of blood tacrolimus concentration after application of the ointment to a large area of the body suggest that the applied area should be as narrow as possible in a barrier-disrupted condition such as erythroderma. However, the safety of tacrolimus ointment has not been established in patients with generalized erythroderma., Conclusions: Tacrolimus concentrations in whole blood should be carefully monitored to prevent nephrotoxicity. Based on the results of that monitoring, the application area and dose of tacrolimus ointment should be closely adjusted, especially in generalized erythrodermic cases.

The clinical differential diagnosis of erythroderma plus immunodeficiency and failure to thrive in neonates includes graft-versus-host-disease (GVHD), Omenn's syndrome (OS), and Netherton's syndrome (NS). In addition to immunological investigations, skin biopsy is an important part of the diagnostic work-up. We reviewed biopsies from 25 patients that were retrieved from the archives of the Department of Histopathology at Great Ormond Street, of which 9 were OS, 11 were GVHD, and 5 were NS. Five patients had two biopsy specimens. Both OS and GVHD show dyskeratosis and basal vacuolation. OS always shows acanthosis and almost always parakeratosis. GVHD shows a flat epidermis and rarely parakeratosis. OS and GVHD can be distinguished after immunohistochemistry for LCA and CD68 by the relative proportions of lymphocytes and macrophages in the dermal infiltrate (predominantly lymphocytes in OS, relatively more macrophages in GVHD). Skin biopsy diagnosis of OS is difficult before 6 weeks of age because the features are poorly developed. NS can be distinguished by psoriasiform acanthosis, thickening of the basement membrane, prominent dermal blood vessels, absence of dyskeratosis, and basal layer vacuolation, and a dermal infiltrate in which lymphocytes and macrophages are equally represented. Thus, the main difference between GVHD and OS is in the proportion of lymphocytes and macrophages in the infiltrate on immunohistochemical staining for LCA and CD68, while OS and NS may be distinguished on H&E morphology alone.

Background: Erythroderma, or generalized erythema of the skin, may result from different causes. At present it is unclear whether the underlying patho-mechanisms that lead to erythroderma are identical or different depending on the original disease. The aim of this study was to investigate the dermal cytokine profile in different types of erythroderma and mycosis fungoides., Methods: Snap-frozen skin biopsy specimens from 33 patients with erythroderma were studied. Thirteen had idiopathic erythroderma, 7 erythrodermic atopic dermatitis, 5 Sézary syndrome and 8 had erythroderma from miscellaneous causes. We also studied 6 patients with mycosis fungoides (5 plaques and 1 tumor) and 5 healthy non-atopic volunteers. The biopsies were immunohistochemically stained for interleukin 4 (IL-4) and interferon gamma (IFN-gamma). All positive cells for IL-4 and IFN-gamma in the dermis were counted and the number of positive cells was calculated per mm2. IL-4/IFN-gamma ratio was calculated for each biopsy., Results: The patients with idiopathic erythroderma, atopic dermatitis and miscellaneous erythroderma, all showed more IFN-gamma-positive cells than IL-4-positive cells in the dermis. The median IL-4/ IFN-gamma ratio for these three groups was 0.6, 0.9 and 0.45, respectively. These differences were not statistically significant. All patients with Sézary syndrome however, showed more IL-4-positive cells than IFN-gamma-positive cells. The median IL-4/IFN-gamma ratio was 1.8, which is significantly higher than in the other groups p<0.05). In mycosis fungoides roughly the same number of cells expressed IL-4 and IFN-gamma. The median IL-4/IFN-gamma ratio was 1.0, which is significantly lower than in Sézary syndrome (p<0.05)., Conclusions: The dermal infiltrate in patients with Sezary syndrome mainly shows a T-helper 2 (Th2) cytokine profile, this in contrast to T-helper 1 (Th1) cytokine profile in benign reactive erythroderma. This indicates that although a relative uniform clinical picture of erythroderma is obvious, a different patho-mechanisms may be underlying.

Background: Erythroderma may result from different causes. At present it is unclear whether the patho-mechanisms that lead to these different types of erythroderma are identical or different. Adhesion molecules and their ligands play a major role in endothelial-leukocyte interactions, which affect the binding, transmigration and infiltration of lymphocytes and mononuclear cells during inflammation, injury, or immunological stimulation. The aim of this study was to investigate the adhesion molecule expression on endothelial cells in erythroderma in situ., Methods: Snap-frozen skin biopsy specimens from 23 patients with erythroderma were studied. Eight had idiopathic erythroderma, 5 erythrodermic atopic dermatitis, 4 Sézary syndrome and 6 had erythroderma from miscellaneous causes. As a control we studied skin specimens from 10 patients with mycosis fungoides, 5 patients with atopic dermatitis and 5 healthy non-atopic volunteers. To determine adhesion molecule expression on endothelial cells in situ, sections were immuno-histochemically double stained with biotinylated Ulex Europaeus agglutinin 1 as a pan-endothelial cell marker, and for the adhesion molecules VCAM-1, ICAM-1, E-, and P-selectin. All double- and single-stained blood vessels in the dermis were counted., Results: Mean endothelial expression in erythroderma was as follows: VCAM-1 51.4%, ICAM-1 70.1%, E-selectin 43.5%, and P-selectin 52.6%. There was no statistical difference between different groups of erythroderma. Mean expression of all adhesion molecules tested, was in Sézary syndrome higher than in mycosis fungoides albeit not significant. In erythrodermic atopic dermatitis only VCAM-1 expression was significantly higher than in lesional skin of atopic dermatitis. No differences were observed in expression of the other three adhesion molecules., Conclusions: There is no difference regarding adhesion molecule expression on endothelial cells between different types of erythroderma.

Background: Exfoliative dermatitis (ED) can result in protein loss due to scaling causing a negative nitrogen balance. Freedberg and Baden (J Invest Dermatol 1962; 38: 277-284) estimated the amount of scale lost in ED by collecting it in an occlusive suit. Subsequently, the nitrogen content was determined by the Kjeldahl method. The exact amount of protein supplementation in ED, dependent on scale loss, is not well established. As occlusion and hyperthermia caused by the suit can inhibit scaling, the objectives of the present study were to design an alternative method to measure the amount of scale lost, to estimate the protein content of the scale, and to propose suitable recommendations for protein supplementation., Methods: In 40 patients with ED, the total protein content lost through scaling per day (P) was determined by the following equation: P = TxIxYxX/25x10(4) g, where T is the total body surface area in square meters, I is the percentage area involved in scaling, estimated using computer-aided design (CAD graph), Y is the amount of scale lost per unit area (0.0025 m2) in milligrams, and X is the quantity of protein present in 1 g of scale in milligrams estimated by a spectrophotometer., Results: It was observed that patients with ED secondary to drug reactions, eczema, and psoriasis lost 7.2, 9.6, and 22.6 g of scale with a protein content of 4.2, 5.6, and 12.8 g respectively. The difference in the amount of protein lost in ED secondary to drug reactions and eczema was not statistically significant; however, the protein lost in psoriasis was significant (p < 0.01 to p < 0.05)., Conclusions: ED may increase the daily protein loss by approximately 25-30% in psoriasis and 10-15% in other causes. Standard treatment for ED and protein supplementation based on our recommendations can minimize the adverse effects of a negative nitrogen balance.

The systemic absorption of topical hydrocortisone (HC) was quantified in seven patients with erythroderma, using the ratio of the areas under the curves for plasma concentration vs. time, following topical and intravenous administration. Over a period of 24 h, 19-93 mg of HC was absorbed systemically, corresponding to 4-19% of the total topical dose of 500 mg. Thus, topical HC therapy of erythroderma is accompanied by a pharmacologically significant systemic dose.

Background: There is no objective laboratory technique to measure and to monitor disease activity in psoriasis., Objective: We assessed the effectiveness of using phosphorus 31 (31P) magnetic resonance spectroscopy (MRS) to noninvasively monitor metabolism in psoriasis and to compare these spectroscopic data with chromatographic analysis., Methods: Fourteen persons were enrolled in the study. 31P magnetic resonance spectra were obtained from skin of persons without skin disease, uninvolved psoriatic skin, nonpsoriatic erythroderma, and from skin of patients with psoriasis. In three patients with psoriasis 31P magnetic resonance spectra were repeated after treatment with methotrexate, UVB, etretinate, and topical steroids. Finally, shave biopsy specimens were obtained from two patients with psoriasis and submitted for chromatographic evaluation., Results: In patients with severe psoriasis, in comparison with the control group, elevations in phosphomonoester concentrations and in the phosphomonoester/phosphodiester ratio were observed. These appear to be useful markers to monitor treatment response in patients with psoriasis. Finally, 31P MRS data in conjunction with chromatographic analysis indicated a defect in phosphometabolism in psoriatic skin. However, it is unclear whether this defect is a cause or an epiphenomenon of the disease., Conclusion: 31P MRS appears to be a sensitive, noninvasive technique to monitor disease activity in psoriasis. Further studies to characterize the defect in phosphometabolism in psoriatic skin are warranted.

Blood and serum glucosaminoglycanes, serum glycosaminoglycane hydrolases, hydroxyprolinuria were measured in 140 patients, 60 of these suffering from psoriasis and 80 from psoriatic arthropathy. A relationship between the severity of impairments of connective tissue metabolism and dissemination of the skin process, as well as activity of articular and visceral inflammations, was examined. The detected regularities are discussed in the light of psoriasis pathogenesis; differential diagnostic potentialities of these regularities are analyzed.

The comparative pattern of 3H-thymidine (3H-T) pulse labelling in lesions of psoriatic erythroderma (3 cases) and of psoriasis vulgaris (20 cases) has been studied by means of radioautography. In the epidermis, no difference was noted between the two types of lesions concerning the epidermal 3H-T labelling index (L.I.) and the localization of labelled cells. The 3H-T L.I. of "round" cells infiltrating the dermis was much higher in lesions of psoriatic erythroderma (4.03 +/- 0.56%) than in lesions of psoriasis vulgaris (0.62 +/- 0.21%), and the difference is highly significant (p less than 0.0001). The findings indicate that most of these labelled cells could well be lymphoblasts, suggesting that an immunological process is possibly involved in the pathogenesis of psoriatic erythroderma.

The distribution and degradation of albumin were determined in twelve patients with extensive skin disease and in ten control subjects by measuring the metabolic turnover and transcapillary escape of 132 I-labelled albumin. The ratio of intravascular to total mass of albumin was normal. Thus the observed hypoalbuminaemia and the low intravascular mass reflect a reduced mass of total body albumin. The rate of synthesis was normal, but the transcapillary escape rate reflecting the microvascular leakiness to macromolecules, and the fractional disappearance rate were significantly higher in the patients than in the controls (P less than 0.001). It is concluded that the hypoalbuminaemia in these patients is the result of an increased endogenous catabolism of albumin without significant loss via urine, stools or skin. A positive correlation between the transcapillary escape rate and fractional catabolic rate of albumin supports the concept of a causal relationship between these parameters.

Feulgen-DNA cytophotometry was carried out in skin imprint preparations of patients with mycosis fungoides, reticulum-cell sarcoma, lymphomatoid papulosis and Sézary's syndrome. These patients proved to have aneuploid and polyploid DNA histograms. In tumour stage of mycosis fungoides a more bimodal distribution of the DNA values was found. Of 79 cases of suspected malignant reticulosis of the skin, 32 showed an abnormal DNA histogram with 5 percent or more tetraploid and hypertetraploid cells. Thirty of these patients developed a malignant skin reticulosis during the 4-year follow-up period. It is concluded that DNA cytophotometry has value as a supplement to routine morphological histopathology in malignant cutaneous reticulosis.

We carried out quantification of the levels of leukotriene B4 (LTB4), a highly potent cell membrane-derived leukocyte chemotactic factor, in scale extracts of psoriasis and related inflammatory dermatoses characterized by sterile subcorneal pustule formation by using radioimmunoassay. A small amount of LTB4 was demonstrable even in extracts from non-inflammatory stratum corneum, but larger amounts were detected in the scale extract from pustular psoriasis and in those from psoriasis vulgaris. There was a significant correlation between the LTB4 and C5a levels in scale extracts, suggesting that complement activation and generation of LTB4 are a closely related event in psoriatic lesions. However, in contrast to highly significant correlation noted between the amount of C5a and chemotactic activity for polymorphonuclear leukocytes (PMN) detectable in scale extracts, LTB4 levels correlated only marginally with the chemotactic activity.

The transcapillary escape rates of albumin (TERalb) and IgG (TERIgG) (i.e. fractions of intravascular masses of albumin and IgG passing to the extravascular spaces per unit time) can be used as parameters of the microvascular leakiness to macromolecules. These parameters were examined simultaneously in 12 patients with extensive skin disease. Six of the patients were reexamined after treatment with systemic steroid. The significantly increased (p less than 0.001) pretreatment values of both TERalb and TERIgG were normalized after treatment with systemic steroid to mean values comparable to those of the control group (p greater than 0.1). The patients mean ratio of TERIgG/TERalb did not differ from that of controls, neither before nor after treatment (p greater than 0.1). The microvascular leakage to differently sized macromolecules in the patients examined seems to be independent of the underlying skin disease. On the background of the structural microvascular changes often described in inflammatory reactions developed experimentally, and the similar changes present in the microvasculature of the psoriatic skin, it is suggested, that the increased microvascular leakage as found in this study, is confined to the postcapillary venules. The functional mechanisms dominating the transport of macromolecules across the vessel wall in this study are compatible with free diffusion as well as with filtration.

Three patients undergoing prolonged total parenteral nutrition at home developed skin lesions, characterized by dryness and scaly appearance, initially confined to the folds but becoming subsequently generalized. Fatty acid measurements in plasma of these patients showed a markedly abnormal lipid pattern: accumulation of 5,8,11-eicosatrienoic acid (20:3omega9) and a high 20:3omega9-to-20:4omega6 ratio. When parenteral fat (Intralipid) was administered, 500 ml/day, serial measurements of fatty acids showed a progressive normalization of the abnormal pattern and a dramatic improvement in the skin lesions. It appears that the daily requirement for linoleic acid in the adult, particularly during the period of rapid anabolism, has not been clearly established. Because more and more patients are becoming partly or totally dependent on parenteral nutrition for prolonged periods of time, the availability of parenteral fat preparations is urgently needed.

In the suspension culture of lymph node cells taken from patients with exzemic erythroderma, an active blast-transformation of lymphocytes starts in 24 hours, whereas in patients with mycosis fungoides this begins only in 48 hours. In lymphocytes taken from patients with mycosis fungoides, a tendency to a slower increase in DNA quantity was noticed compared to that in patients with exzemic erythrodermy. The differences observed may be used for diagnostic purposes.

The fibrous protein of stratum corneum was isolated from a patient with bullous congenital ichthyosiform erythroderma (BCIE), and its properties characterized using electron microscopy, amino acid analysis and SDS gel electrophoresis. Results were compared with the characteristics of the fibrous protein isolated from stratum corneum of normal controls. From 900 mg (dry weight) of stratum corneum, 68 mg of fibrous protein was obtained from the patient, while 178 mg was obtained from the normal control. Structural differences were observed with electron microscopy and chemical differences, were shown in the ratio of several amino acids. On SDS electrophoresis, the 55,000 dalton constituent of normal fibrous protein could not be identified in the fibrous protein from this patient. These results suggest that an alteration of the polypeptide composition of fibrous protein from this patient with BCIE occurred, and this alteration induced the morphological and clinical features of this dominant genetic keratinization disorder.

A patient had Sézary syndrome and lymphocytic lymphoma. Cytoplasmic inclusions within the Sézary cells were demonstrated by histochemistry and electron microscopy to be composed of fetal-type glycogen. Results of tests for the presence of virus were negative. It is suggested that the Sézary cell represents a reversion of metabolic systems to more youthful types. Previously reported differences in diastase reactivity of the PAS-positive cytoplasmic inclusions are probably based on whether the glycogen is in fetal or mature configuration.