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[Erythroderma with immunoglobulin deposits along the basal membrane. Pemphigoid erythroderma?].

INTRODUCTION: There are many clinical forms of bullous pemphigoid. Nodular, localised, vegetating, vesicular and dysidrosiform variants have been described. The appartenance to the spectrum of pemphigoid was confirmed by the demonstration of antibodies directed against the 230 and 180 kDa BP antigens. Three cases of erythrodermic pemphigoid were recently described. OBSERVATIONS: We describe two cases of patients suffering from erythroderma for several months associated with a linear deposit of immunoglobulins and complement along the basement membrane. In the first observation, the patient suffered from bullae of the legs before developing erythroderma. The positive direct immunofluorescence of the skin was associated with circulating anti basement membrane antibodies, making therefore the diagnosis of erythrodermic pemphigoid possible. In the second case, the patient never developed blisters. We also found a linear deposit along the basement membrane, localized on the dermic side of a skin treated by molar NaCl. No circulating antibodies were found by indirect immunofluorescence or by immunoblott. Direct immuno electron microscopy showed a deposit of immunoglobulins into the deep layers of the lamina lucida and into a part of the lamina densa. CONCLUSION: These two cases suggest that there are true erythrodermic pemphigoid without blisters. The value of the systematic direct immunofluorescence examination of the skin of erythroderma should be evaluated.

Aged↗

The incidence of erythroderma: a survey among all dermatologists in The Netherlands.

BACKGROUND: Erythroderma is a rare skin disorder, and studies on its incidence and causes are lacking. The annual incidence has been estimated to be 1 to 2 patients per 100,000 inhabitants. OBJECTIVE: We investigated the incidence and cause of erythroderma in an unselected population and evaluated the referral pattern of erythrodermic patients by nonacademic dermatologists. METHODS: A survey was performed among all nonacademic dermatologists in The Netherlands, using a mailed questionnaire. Questions dealt with the number of patients diagnosed with erythroderma in the year 1997, the cause of the erythroderma, and whether these patients were referred to a university hospital. A questionnaire was also sent to all university hospitals. RESULTS: Seventy-eight percent of the nonacademic dermatologists answered the questionnaire, and all 8 university hospitals responded. In the year 1997, 141 patients were diagnosed with erythroderma in The Netherlands. The annual incidence of erythroderma based on these figures is 0.9 patients per 100,000 inhabitants. Compared with the university hospitals, erythroderma was more often diagnosed as an exacerbation of preexisting dermatoses (61% vs 51%; P =.37) and less often as idiopathic (14% vs 31%; P =.04) among the nonacademic dermatologists. Cutaneous T-cell lymphoma was rarely the cause, occurring in only 1% of patients diagnosed by the nonacademic dermatologists but in 6% of patients at the university hospitals. Overall, only 37% of nonacademic dermatologists referred patients with erythroderma to a university hospital. CONCLUSIONS: The incidence of erythroderma in The Netherlands is slightly lower than the earlier estimate in the literature. Moreover, the cause of erythroderma is different among patients diagnosed in an academic and a nonacademic setting. The majority of dermatologists in The Netherlands treat patients with erythroderma themselves and do not refer these patients to university hospitals.

Adult↗

Interleukin 4 and interferon-gamma expression of the dermal infiltrate in patients with erythroderma and mycosis fungoides. An immuno-histochemical study.

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.

Antibodies, Monoclonal↗

Erythroderma. A clinicopathological study of 56 cases.

BACKGROUND AND DESIGN: Erythroderma may be the result of many different causes. There are several publications on this subject, most of them from England, the United States, and the Scandinavian countries reporting a different incidence of each etiologic group. Our objective has been to determine the frequency of erythroderma in our environment, its cause, and patient evolution. We reviewed the clinical, laboratory, and biopsy material of 56 patients diagnosed with erythroderma who were treated in our department in the last 8 years (1984 through 1991). Patients were followed up to know the evolution of the erythroderma. RESULTS: The male-female ratio was 4:1. The mean age at diagnosis was 57 years. Dermatoses were the most frequent cause of erythroderma (62.5%), followed by topical or systemic drug reactions (16%), and cutaneous T-cell lymphomas (12.5%). Follow-up information was obtained from 42 patients (66%). Eight patients died (19%), but only in three cases was death directly related to erythroderma (7.14%). The group associated with the best prognosis was that related to drugs. The best clinicohistologic correlation was found in cutaneous T-cell lymphoma-related erythroderma. CONCLUSIONS: Erythroderma of unknown cause and protracted course may be secondary to senile atopic dermatitis, intake of drugs overlooked by the patients, and patients who are in slow progression to cutaneous T-cell lymphoma. Close follow-up of erythrodermas of unknown cause by repeating cutaneous biopsies will in time allow an early diagnosis in patients in the latter group.

Blood Sedimentation↗

Expression of VCAM-1, ICAM-1, E-selectin, and P-selectin on endothelium in situ in patients with erythroderma, mycosis fungoides and atopic dermatitis.

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.

Cell Adhesion Molecules↗

[Erythroderma induced by hypercalcitoninemia: two cases].

INTRODUCTION: The most common cause of erythroderma is the extension of a previous cutaneous disease to the entire skin surface, as is the case in mycosis fungoides or drug reactions. Erythroderma related to endocrine disorders has only exceptionally been published. We report two cases of patients suffering from erythroderma probably induced by hypercalcitoninemia. OBSERVATIONS: Case 1. A 69 year-old man had a two year-history of fluctuating erythroderma, resistant to all topical or systemic therapy. After numerous unsuccessful investigations, a high serum calcitonin rate was detected. The pentagastrin test was highly positive, suggesting a medullar carcinoma of the thyroid. Thyroidectomy showed only hyperplasia of C cells. All skin signs disappeared within a few days after surgery. Two years later, there was no recurrence of the erythroderma and the serum calcitonin rate was normal. Case 2. A 58 year-old man suffered from congestive and pruriginous erythroderma for 2 1/2 months, which responded well to topical steroids. Biological investigations done for flushes, showed a raised calcitonin level and highly positive pentagastrin test. Thyroidectomy also revealed simple hyperplasia of the C cells. No recurrence of the erythroderma was noted during the 6 month follow-up. DISCUSSION: These are the first cases of erythroderma associated with hypercalcitoninemia. The causal role of calcitonin is probable in the first case, because of 1) long duration of skin signs before the hypercalcitoninemia; 2) quick post-operative recovery, in parallel with the decrease in calcitonin level; 3) absence of recurrence after thyroidectomy; 4) absence of other proven causes. Erythroderma may have resulted from dilation of the skin vessels, since calcitonin and calcitonin gene related peptide are powerful vasodilators.

Aged↗

Idiopathic erythroderma: a follow-up study of 28 patients.

BACKGROUND: Erythroderma may result from different causes, but a proportion remains undetermined (idiopathic erythroderma). Patients with idiopathic erythroderma have often been regarded to have a pre-Sézary syndrome because some of these patients have developed a cutaneous T-cell lymphoma during follow-up. OBJECTIVE: The aim of this study was to investigate if this was true for our group and also if it is possible to identify further which patients are at high risk of developing cutaneous T-cell lymphoma. METHODS: We analyzed clinical and follow-up data and reviewed the skin histopathology of all patients who were diagnosed with idiopathic erythroderma in our clinic between 1977 and 1994. RESULTS: Twenty-eight patients, 16 males and 12 females, were diagnosed with idiopathic erythroderma. This is 27% of the patients who were diagnosed with erythroderma in our clinic, during this period. During the median follow-up of 33 months, 35% of the patients went into complete remission and 52% showed partial remission. Three patients (13%), all females, had persistent chronic erythroderma. Two of the latter group progressed to cutaneous T-cell lymphoma, i.e. 1 to Sézary syndrome and 1 to mycosis fungoides. CONCLUSION: Based on our results we conclude that only patients with persistent chronic idiopathic erythroderma, which is a minority, have an increased risk of developing cutaneous T-cell lymphoma and therefore need a close and long-term follow-up.

Adult↗

Neonatal and infantile erythrodermas: a retrospective study of 51 patients.

OBJECTIVE: To determine the frequency of the various underlying causes of erythroderma in newborns or infants, as well as which clinical or laboratory findings were relevant for the etiological diagnosis. PATIENTS: Fifty-one patients who presented with exfoliative erythroderma during their first year of life were included in this retrospective study. SETTING: Department of Pediatric Dermatology at a university hospital. RESULTS: On average, the etiological diagnosis was established 11 months after the onset of erythroderma. The underlying causes observed included immunodeficiency (30%), simple or complex ichthyosis (24%), Netherton syndrome (18%), and eczematous or papulosquamous dermatitis (20%). Five patients (10%) had erythroderma of unknown origin. The following parameters were of value in determining the underlying cause of erythroderma: congenital onset, skin induration and the presence of large scaling plaques, alopecia with or without hair dysplasia, evolution, response to topical corticosteroid therapy, presence of infections, and failure to thrive. Histological analysis confirmed the diagnosis in only 19 (45%) of 42 cases. However, it proved of great value for the detection of significant lymphocyte infiltration or keratinocyte necrosis indicating a diagnosis of Omenn syndrome or immunodeficiency. The prognosis was poor in this series: the mortality rate was 16%, and severe dermatosis persisted in 29 (67%) of the survivors. CONCLUSIONS: The etiological diagnosis of neonatal erythroderma is difficult to make; some clinical features may be helpful, but no one feature is characteristic of a cause. An immunodeficiency must be suspected in cases of severe erythroderma with skin induration, severe alopecia, failure to thrive, infectious complications, or evocative histological findings. The prognosis is poor, with a high rate of mortality in immunodeficiency disorders and severe chronic disease in Netherton syndrome and psoriasis.

Dermatitis, Exfoliative↗

Monoclonal T-cell dyscrasia of undetermined significance associated with recalcitrant erythroderma.

BACKGROUND: Erythroderma is a diffuse, inflammatory skin reaction that, in rare instances, is associated with hematologic malignancies such as cutaneous T-cell lymphoma (erythrodermic mycosis fungoides) or T-cell leukemia (Sezary syndrome or adult T-cell leukemia/lymphoma). OBSERVATIONS: We screened 30 patients with erythroderma (20 patients with erythroderma of known etiology and 10 patients with idiopathic erythroderma) for the presence of circulating monoclonal T-lymphocyte populations using T-cell receptor (TCR)-gamma gene-specific polymerase chain reaction and automated capillary DNA electrophoresis. Moreover, the phenotypic analysis of peripheral blood CD4+ lymphocytes was performed using the following surface markers: CD3, CD7, CD8, CD25, CD26, CD27, CD28, CD29, CD30, CD45RO, CD45RA, CD56, CD134, HLA-DR, TCRalphabeta, TCRgammadelta, and cutaneous lymphocyte antigen (CLA). In 5 patients with idiopathic erythroderma we detected T-cell clones in peripheral blood (in 1 case, associated with the presence of the same clone in the skin) and a 2-fold increase in the proportion of CD3+ CD4+ CD7- CD26- cells. Cell depletion studies indicated that the monoclonal T cells were present within the CD4+ CD7- cell population. Clinically, all patients had chronic, recalcitrant erythroderma but none developed any hematological malignancy during their lifetimes or fulfilled the criteria for cutaneous lymphoma or Sezary syndrome. CONCLUSIONS: A proportion of patients with chronic erythroderma present with the monoclonal expansion of CD4+ CD7- CD26- lymphocytes in their blood. This condition represents a probably benign T-cell dyscrasia, or one of very low malignancy. Alongside monoclonal gammapathy of undetermined significance (MGUS) and monoclonal (B-cell) lymphocytosis of undetermined significance (MLUS), we propose using monoclonal T-cell dyscrasia of undetermined significance (MTUS) to underline a conceptual similarity between this disorder and the more common types of lymphocytic dyscrasia.

Adult↗

Life-threatening erythroderma: diagnosing and treating the "red man".

Exfoliative erythroderma, or diffuse erythema and scaling of the skin, may be the morphologic presentation of a variety of cutaneous and systemic diseases. Establishing the diagnosis of the underlying disease is often difficult and, not uncommonly, erythroderma is classified as idiopathic. Several cases are presented to demonstrate the diversity of presentation of this disease. Laboratory findings are typically unhelpful in establishing the etiology of erythroderma. Clinical data combined with multiple skin biopsies over time are necessary. Systemic complications of erythroderma include infection, fluid and electrolyte imbalances, thermoregulatory disturbance, high output cardiac failure, and acute respiratory distress syndrome. The initial approach to the management of erythroderma of any etiology includes attention to nutrition, fluid and electrolyte replacement, and the institution of gentle local skin care measures. Oatmeal baths and wet dressings to weeping or crusted sites should be followed by application of bland emollients and low-potency topical corticosteroids. Systemic dermatologic therapy may be required to maintain improvement achieved with local measures or to control erythroderma refractory to local measures. The prognosis of erythroderma is dependent on the underlying etiology.

Adult↗

Erythroderma. A clinical and follow-up study of 102 patients, with special emphasis on survival.

BACKGROUND: Erythroderma may result from different causes. There have been no publications on this subject with special emphasis on survival. OBJECTIVE: The aim of the study was to determine the cause of the erythroderma and the prognosis of these patients. METHODS: Clinical and follow-up data from 102 patients with erythroderma were analyzed. We estimated survival of patients with erythroderma, from causes other than Sézary syndrome, mycosis fungoides, or leukemia cutis. The survival was compared with that of an age-matched control group of the general population. RESULTS: The main cause of erythroderma was exacerbation of a preexisting dermatosis (53%). Drug reactions were rarely the cause (5%). A high proportion of the patients had chronic actinic dermatitis/actinic reticuloid (12%). Survival of men with erythroderma was significantly lower than that of the general population. CONCLUSION: Men with erythroderma, from causes other than Sézary syndrome, mycosis fungoides, or leukemia cutis, have a lower survival than men in the general population.

Adolescent↗