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Pseudoxanthoma elasticum (PXE) is a systemic disorder affecting elastic tissues most markedly in skin, retina, and blood vessels. It is caused by mutations in the ABCC6 gene and is transmitted in an autosomal recessive fashion. In 1994 a new classification system for PXE was published as the result of a consensus conference. Since then the ABCC6 gene has been discovered. We propose that there is a need for a classification system incorporating all relevant systemic symptoms and signs, based on standardized clinical, histological, and molecular biological examination techniques. We re-evaluated the histopathologic PXE signs and propose a classification system with unambiguous criteria leading to a consistent diagnosis of definitive, probable, or possible PXE world-wide. We put this proposed classification forward to encourage further debate on the diagnosis of this multi-organ disorder. (c) 2010 Wiley-Liss, Inc

Purpose: Pseudoxanthoma elasticum is an autosomal recessive disorder of elastic tissue in the skin, eyes, and cardiovascular system, caused by mutations in the ABCC6 gene. The purpose of this study was to check variability in expression within one genotype and look for pseudoxanthoma elasticum signs in heterozygotes. Methods: We examined a relatively large, in comparison with the present literature, group of adult persons homozygous or heterozygous for the c.3775delT mutation in the ABCC6 gene, front a genetically isolated population in the Netherlands. All participants filled out a questionnaire and underwent standardized dermatologic and ophthalmologic examinations with photography of skin and fundus abnormalities. Skin biopsies from affected skin or a predilection site and/or a scar were examined and compared with biopsies from controls. Results: Skin abnormalities, ophthalmologic signs, and cardiovascular problems varied greatly among the 15 homozygous participants. There was no correlation among severity of skin, eyes, or cardiovascular abnormalities. None of the 44 heterozygous participants had any sign of pseudoxanthoma elasticum on dermatologic, histopathologic, and/or ophthalmologic examination, but 32% had cardiovascular disease. Conclusion: Individuals homozygous for the c.3775delT mutation can have a highly variable phenotype. We did not find pseudoxanthoma elasticum eye or skin abnormalities in the heterozygous family members. Genet Med 2009:11(12):852-858

In dit artikel worden enkele huidaandoeningen besproken die relatief weinig voorkomen en, doordat ze zich onder verschillende beelden kunnen presenteren, vaak moeilijk te herkennen zijn: erythema exsudativum multiforme, erythema nodosum, lichen planus en granuloma annulare.

Contains fulltext : 32422.pdf (Publisher’s version ) (Closed access) Pseudoxanthoma elasticum (PXE) is a heritable disorder of connective tissue, affecting mainly skin, eye and the cardiovascular system. PXE is characterized by dystrophic mineralization of elastic fibres. The condition is caused by loss of function mutations in ABCC6. We generated Abcc6 deficient mice (Abcc6-/-) by conventional gene targeting. As shown by light and electron microscopy Abcc6-/- mice spontaneously developed calcification of elastic fibres in blood vessel walls and in Bruch's membrane in the eye. No clear abnormalities were seen in the dermal extracellular matrix. Calcification of blood vessels was most prominent in small arteries in the cortex of the kidney, but in old mice, it occurred also in other organs and in the aorta and vena cava. Newly developed monoclonal antibodies against mouse Abcc6 localized the protein to the basolateral membranes of hepatocytes and the basal membrane in renal proximal tubules, but failed to show the protein at the pathogenic sites. Abcc6-/- mice developed a 25% reduction in plasma HDL cholesterol and an increase in plasma creatinine levels, which may be due to impaired kidney function. No changes in serum mineral balance were found. We conclude that the phenotype of the Abcc6-/- mouse shares calcification of elastic fibres with human PXE pathology, which makes this model a useful tool to further investigate the aetiology of PXE. Our data support the hypothesis that PXE is in fact a systemic disease.

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 Sezary 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 Sezary 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

Purpose: Granulomatous slack skin (GSS) is a rare cutaneous disorder characterized clinically by the evolution of circumscribed erythematous lax skin masses, especially in the body folds, and histologically by a granulomatous T-cell infiltrate and loss of elastic fibers. GSS is often associated with preceding or subsequent lymphoproliferative malignancies, especially mycosis fungoides (MF) and Hodgkin’s disease (HD). No effective treatment is known yet. Whether this entity is a benign disorder, a peculiar host reaction to a malignant lymphoma, a precursor of malignant lymphoma or an indolent cutaneous T-cell lymphoma (CTCL) in itself is still a matter of debate. Patients and Methods: The results of the patients with GSS from the Netherlands are compared with the cases reported in the world literature. Results: A female patient had had GSS for 8 years without developing a secondary malignancy. In a second female patient with a histologically confirmed diagnosis of MF, GSS developed 18 years later in the axillary and inguinal folds which had previously been affected by plaque-stage MF lesions. A third male patient with a 6-year history of erythematosquamous skin disease diagnosed as CTCL developed GSS. Moreover, granuloma formation was also found in a facial basal cell carcinoma, in a cervical lymph node and the spleen. Clonal rearrangements of the T-cell receptor β genes were found in the 2 female patients; the male patient could not be tested. Conclusion: GSS is a rare clinicopathological entity. Only 34 patients have been described so far. The development of GSS within plaque MF lesions has not been reported before. Our third case developed very extensive skin lesions and showed a strong propensity to develop granulomas as compared to cases reported before. The presence of a clonal T-cell population was demonstrated in all cases tested. Our cases support the idea that GSS is a very rare and rather indolent type of CTCL. Apparently, the disease is associated with a peculiar immune response, characterized by granuloma formation and disappearance of elastic fibers resulting in the lax skin. The relationship between GSS and other preexisting or subsequent lymphoproliferative diseases (diagnosed in approximately 50% of the cases) warrants a life-long follow-up.

A 33-year-old woman presented with a 4-week history of a painless swelling of her left ear. She denied a blunt trauma or a freezing episode. There was no local redness or suppuration, and no problems in joint. Her medical history was unremarkable, except for migraine. On examination the cranial part of the helix of the left ear, spreading to the adjacent antehelix had a soft subdermal bulgy swollen appearance with a slightly bluish colour (figure 1). …

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 Se´zary 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 Se´zary syndrome, mycosis fungoides, or leukemia cutis, have a lower survival than men in the general population.

A hitherto unreported variant of mammary Paget's disease (MPD) limited to the areola, leaving the nipple unaffected, has been analyzed by serial sectioning of the whole areola and nipple. This otherwise characteristic MPD proved to be confined to the epidermis. There was no underlying carcinoma. This MPD was associated with a multifocal presence of monomorphic but otherwise similar cells in small collections surrounding the ostia of areolar mammary glands in the clinically unaffected area. This condition was interpreted as hyperplasia of mammary gland-related cells also found in normal nipples (so-called Toker cells). The observations hint at a possible derivation of some cases of mammary and extramammary Paget's disease from such Toker cells.

BACKGROUND AND DESIGN The hyperimmunoglobulinemia D (hyper-IgD) syndrome is characterized by recurrent febrile attacks with abdominal distress, headache, and arthralgias. Physical examination reveals cervical lymphadenopathy in most cases and, sometimes, splenomegaly. Skin lesions have been observed in isolated cases during attacks. We summarize the features of skin lesions and the histopathologic findings in biopsy specimens in the hyper-IgD syndrome. RESULTS A total of 44 patients with the hyper-IgD syndrome were studied. Thirty-five (79%) of them, 19 males and 16 females, had skin lesions during febrile attacks. Erythematous macules were the most common cutaneous manifestation (15 cases), followed by erythematous papules (12 cases); urticarial lesions (nine cases) and erythematous nodules (seven cases). Skin biopsy specimens of 10 patients with the hyper-IgD syndrome were available for review. The findings varied considerably. Most biopsy specimens showed mild features of vasculitis. Nonspecific findings were noted in five biopsy specimens; Sweet-like features in two, cellulitis-like findings in one, and deep vasculitis characteristics in one. CONCLUSIONS Skin lesions are common in the hyper-IgD syndrome suggesting that they are a true manifestation of the disease.

Background and Design: The hyperimmunoglobulinemia D (hyper-IgD) syndrome is characterized by recurrent febrile attacks with abdominal distress, headache, and arthralgias. Physical examination reveals cervical lymphadenopathy in most cases and, sometimes, splenomegaly. Skin lesions have been observed in isolated cases during attacks. We summarize the features of skin lesions and the histopathologic findings in biopsy specimens in the hyper-IgD syndrome. Results: A total of 44 patients with the hyper-IgD syndrome were studied. Thirty-five (79%) of them, 19 males and 16 females, had skin lesions during febrile attacks. Erythematous macules were the most common cutaneous manifestation (15 cases), followed by erythematous papules (12 cases), urticarial lesions (nine cases) and erythematous nodules (seven cases). Skin biopsy specimens of 10 patients with the hyper-IgD syndrome were available for review. The findings varied considerably. Most biopsy specimens showed mild features of vasculitis. Nonspecific findings were noted in five biopsy specimens; Sweet-like features in two, cellulitislike findings in one, and deep vasculitis characteristics in one. Conclusions: Skin lesions are common in the hyper-IgD syndrome suggesting that they are a true manifestation of the disease. (Arch Dermatol. 1994;130:59-65)

Familial occurrence of Jessner's lymphocytic infiltration of the skin is reported in a father and daughter. A definitive diagnosis of Jessner's disease was greatly facilitated by the presence of large numbers of plasmacytoid monocytes within the dermal infiltrates in both patients. A role for skin-directed lymphocyte migration is suggested to account for the presence of this peculiar cell type.

SUMMARY Skin biopsies of 31 non-atopic patients, 20 with mycosis fungoides, six with psoriasis and five with contact dermatitis, and of five non-atopic healthy controls were compared for the presence of cell-bound IgE and vacant IgE binding sites. IgE+ cells were demonstrated in the cutaneous infiltrate of nine (45%) patients with mycosis fungoides, two (33%) with psoriasis and one (20%) with contact dermatitis. Following pre-incubation of skin sections wilh IgE myeloma protein to saturate vacant IgE-binding sites, 14 out of 16 patients (88%) with stage I mycosis fungoides, five (83%) patients with psoriasis and one (20%) with contact dermatitis showed an increase in the number of IgE+ cells. While cell-bound IgE was positively related to serum IgE levels the expression of IgE-binding sites was not. All IgE+ cells were HLA-DR+ dendritic cells identified as either macrophages (CD68+, CDI4+) or Langerhans cells (CDl+). Skin biopsies of non-atopic healthy controls or clinically uninvolved skin in mycosis fungoides had neither any IgE+ cells nor any vacant binding sites. Inhibition studies with IgGl, IgG4 and IgE myeloma proteins as well as with several enzymatic fragments of igE demonstrated that IgE interacled with Fcɛ-receptors through isotype-specific structures on the Fcɛ-fragment. Four anti-CD23 monoclonal antibodies, however, were unuble to stain vacant Fcɛ-receptors nor could they block IgE-binding. We hypothesize that locally-secreted lymphokines, like IL-4 or interferon-γ, induce Fcɛ-receptors on dendritic cells in the cutaneous infiltrate and that these receptors become occupied in parallel wilh elevated serum IgE levels.

Diagnostic image (393). A boy with a white rim around a birth mark.- A 6-year-old boy presented with a congenital halo naevus naevocellularis.

An animal experiment is presented in which two groups of pigmented hairless mice were exposed daily to suberythemal doses of UVA to study tumourigenesis. The aim of the study was to estimate the carcinogenic risks of tanning by UVA. The pigmented hairless mice, Skh-hr2, were separated by selective breeding into two groups, the "browns" and the "blacks". Both groups were exposed daily to UVA from fluorescent UVA lamps (Philips TL40W/09) purified by rigorously filtering out the shorter wavelengths. No acute actinic damage was observed after any exposure. However, in most UVA exposed animals, especially in the blacks, a marked scratching preceded the development of tumours. Hyperkeratosis was also observed. All animals developed tumours. Histopathologically at least 60% of the tumours were squamous cell carcinomas. Depositions of melanophages were observed, but no melanomas. It is beyond any doubt that UVA is carcinogenic in laboratory animals. The present state of knowledge justifies no preference for tanning with UVA over tanning with UVB.

A 58-year-old man with renal insufficiency, who was being treated by haemodialysis, developed progressive skin lesions. He had thickening and hardening of the skin at the extremities and swelling of the toes and fingers with flexion contractures. His face was not affected. Laboratory evaluation was unremarkable and a skin biopsy [table: see text] showed an increase of collagen and mucin, without an inflammatory infiltrate. These clinical features resemble a recently reported new disorder: nephrogenic fibrosing dermopathy. This disorder manifests as scleromyxedema-like cutaneous skin lesions without associated paraproteinemia, occurring in the setting of renal disease. The histopathologic features of nephrogenic fibrosing dermopathy, i.e. thickened collagen and mucin deposition, are unique. The incidence, prevalence and cause of the disease are unknown and there is currently no effective treatment. The Centers for Disease Control and Prevention (CDC) in the USA are calling on physicians who have encountered patients suffering from this type of lesions to contact the CDC for an intended control study.

SummaryBackground There is a clear relationship between ultraviolet (UV) radiation (UVR) and the clinical manifestations of patients with lupus erythematosus (LE). Cutaneous lesions are induced or exacerbated by exposure to UVR. Of patients with LE, 24–83% are reported to be photosensitive to UVR. LE tumidus appears to be the most photosensitive subtype of LE, followed by subacute cutaneous LE (SCLE). In general, the history of patients with LE correlates poorly with the presence or absence of photosensitivity, due to a delayed time interval between UV exposure and exacerbation of skin lesions. Phototesting using artificial UVR and visible light is a reliable way of diagnosing photosensitivity. Objectives To investigate the photoreactivity of patients with various subtypes of LE using an individualized phototest protocol. The results of phototests were correlated with the history of photosensitivity, the subtype of LE, the presence of autoantibodies and the use of anti-inflammatory medication by these patients. Methods Phototesting with UVA, UVB and visible light was performed in 100 patients with LE. The diagnosis of LE was established both on clinical examination and skin histology. Serological studies were also performed in all patients. The phototests were performed on large skin areas of the forearm or trunk; the first dose was twice the minimal erythema dose and the dosage was increased according to the individual reactions of the patients at the test sites. Follow-up of skin reactions at the test sites was performed for up to 2 months. Histological examination of the photoprovoked skin lesions was carried out in 57 patients. Results Of the 100 patients included (81 women and 19 men; mean age 41 years, range 17–79), 46 had chronic discoid LE, 30 SCLE and 24 systemic LE. An abnormal reaction to UVR and visible light was found in 93% of our patients with LE. No clinical or histological evidence at the phototest sites of polymorphic light eruption was found. There was no correlation between photosensitivity and LE subtype, presence of autoantibodies or medical history. Concomitant use of anti-inflammatory medication seemed to exert only minimal influence on the results of phototesting. Conclusions When using an extended phototesting protocol, almost all patients with LE in this study showed clinical and histological evidence of aberrant photosensitivity. Therefore, patients with LE should receive thorough advice and instruction on photoprotective measures, regardless of their history, LE subtype or presence of autoantibodies.

Background: Treatment of early-stage mycosis fungoides (MF) consists of topical steroids, phototherapy (UVB), photochemotherapy (psoralen plus UVA [PUVA]), topical nitrogen mustard, or total skin electron-beam irradiation. It has been reported that the same effective UVB dose is safer than PUVA regarding carcinogenicity and produces fewer side effects. Narrowband UVB (311 nm) results in less irritation and erythema and is more effective compared with broadband UVB. Objective: Our purpose in this retrospective study was to analyze the response to treatment, relapse-free interval, and irradiation dose in 56 patients with early-stage MF (stage Ia and Ib). A total of 21 patients were treated with narrowband UVB (311 nm); 35 patients were treated with PUVA. Results: Narrowband UVB treatment led to complete remission in 17 of 21 patients (81%), partial remission in 4 of 21 (19%), and none showed progressive disease. PUVA treatment led to complete remission in 25 of 35 patients (71%), partial remission in 10 of 35 (29%), and none showed progressive disease. The mean relapse-free interval for patients treated with UVB was 24.5 months (range, 2-66 months) and for patients treated with PUVA, 22.8 months (range, 1-43 months). Conclusion: Narrowband UVB therapy for patients with early-stage MF is an effective treatment modality. It has several advantages over treatment with broadband UVB and PUVA. When treating patients with early-stage MF it may be beneficial to start with narrowband UVB therapy and, if there is progression or no response, switch to PUVA therapy. (J Am Acad Dermatol 2003;48:215-9.)

This paper presents a new method for the capture, analysis, and classification of radio transmitter transients. This method involves the use of a capturing subsystem consisting of an Icom IC-R7000 communications receiver and a Sound Blaster 16 sound card running on a PC. The radio transients are sampled at 44,100 samples per second and have 16 bits accuracy. Once the transmitter transient has been captured, a genetic algorithm selects the critical features from the wavelet coefficients for classification. The selected wavelet coefficients are considered to be fingerprints, and are presented to a back propagation neural network for transmitter classification. The capturing and analysis system, ODO-1, is able to classify both transients of the same model type as well as individual transmitters with 100% accuracy on a small data base of transmitter fingerprints.

This paper presents a method of generating unique fingerprints of radio transmitter turn-on transients. The fingerprinting system consists of the application of multiresolution wavelet analysis used to characterize the features contained in the transient followed by the use of a genetic algorithm to extract the wavelet coefficients that represent critical features of the transient. To measure the ability of the system to generate efficient and unique fingerprints, a neural network is used to classify the transients by their fingerprints. To test the noise sensitivity of the system, noisy transients were applied to a trained neural network, the network was able to positively classify noisy transients with 20 dB signal to noise ratios (SNR) and up. Experiments with real radio transients show that the system is able generate uniqiue fingerprints for absolute classification by a neural network for radios of differing model type as well as radios of the same model type.

Lymphomatoid papulosis (LyP) is a chronic recurrent self-healing condition, with histological features suggestive of a malignant lymphoma. Only a few cases have been described in children. We report 10 children with this skin disease and compare them with the adult type of LyP and childhood cases described in the literature. Although LyP has the same clinical picture and histology in both age groups, in contrast with the adult type no transformation into malignancy has been described in childhood.

Objective: Case report to illustrate that non-healing ulcers should be rigorously investigated to exclude the possibility of malignant neoplasm. Setting: University Hospital, Utrecht, The Netherlands. Patients: One 62-year-old patient presenting with a 3 month history of leg ulcer. Interventions: Diagnostic biopsy followed by radiotherapy and chemotherapy. Results: Histological examination of the biopsy demonstrated a B-cell lymphoma which showed no recurrence during an 8-year follow up-period after treatment. Conclusion: Primary cutaneous lymphoma is a rare cause of malignancy mimicking venous leg ulceration.

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 Sezary 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 Sezary 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.

Polymorphous light eruption is a common chronic idiopathic photodermatosis. The action spectrum and therapy are under debate.The aim of the study was to analyze the clinical aspects of this dermatosis, the photodiagnostic tests, and the results of therapy in an academic center.To obtain a reasonable follow-up period, we examined all available data of the patients who underwent diagnostic phototests in the period 1985 through 1991. Our procedure of phototesting included determination of minimal erythema doses, photoprovocation tests, and photopatch tests. The evaluation of the effect of the therapy was based on the patients' experiences, time spent outdoors, and amount of sun exposure.Our collection included data on 35 men and 75 women. The age at onset differed significantly between men and women (averages 46 and 28 years, respectively; P.01). The minimal erythema doses for UVB were lowered in 43% of the men and in 4% of the women (P.01); the minimal erythema doses for UVA were lowered in 37% of the men and in 11% of the women (P.01). The photoprovocation tests showed a pathologic reaction to both UVB and UVA in 88% of the men and in 52% of the women (P.01). In the remaining patients we found pathologic reactions to UVB alone (for men 9%, for women 24%; P.05) or UVA alone (for men 3%, for women 24%; P.01). The abnormal reactions to visible light were almost exclusively observed in those patients who reacted pathologically to both UVB and UVA (43% of the male patients, 11% of the female patients; P.01). The photopatch tests showed a large number of positive test results, mainly to skin care products or sunscreens (75% of all patients). The 70 most sensitive patients (64%) were treated with prophylactic UVB therapy 2 or 3 times a week at home or initially in the outpatient department. This treatment was normally done from February to June, but in severe cases throughout the whole year.Phototests revealed abnormal reactions to UVB as well as UVA and to some extent also to visible light. Prophylactic UVB therapy is a successful treatment for polymorphous light eruption.

In patients with primary cutaneous B-cell lymphomas (CBCL) and primary cutaneous T-cell lymphomas (CTCL), extracutaneous sites may become involved and then polychemotherapy is indicated. Multi-agent chemotherapy may induce long lasting complete remissions in CBCL's. Most CTCL's, especially mycosis fungoides (MF), and CD30 negative primary cutaneous large T-cell lymphoma (PCLTCL) respond poorly or partially to Multi-agent Chemotherapy.We have studied whether cutaneous lymphomas express the following multidrug resistance (MDR) related proteins: multidrug resistance protein (MRP), lung resistance protein (LRP) and P-glycoprotein (Pgp).From the files of the Dutch Cutaneous Lymphoma Working Group we selected pretreatment punch biopsy specimens of the skin from 14 patients with MF, 10 patients with a PCLTCL and 8 patients with a CBCL. In several patients with a clinical relapse of their disease after multi-agent chemotherapy, punch biopsy specimens of cutaneous lesions were available (6 MF, 3 PCLTCL, 1 CBCL). Benign dermatoses with a dense lymphoid infiltrate were included as a control. Immunohistochemistry was done on formalin fixed, paraffin-embedded punch biopsy specimens with monoclonal antibodies MRPrl (anti-MRP); LRP-56 (anti-LRP); C219 (anti-Pgp). Staining was performed by the biotin-streptavidin immunoperoxidase method.MRPrl staining was found in the cytoplasm ofor = 5%-50% of lymphoid cells in 13 out of 14 cases of MF and in 6 out of 10 patients with a PCLTCL. In 2 out of 8 cases of CBCLor = 5%-50% positive tumorcells were found. Strong staining (or = 50% of the cells positive) was found in 10 out of the total of 24 CTCL cases. LRP56 staining of lymphoid cells was found in 1 out of 14 cases of MF and in 1 out of 10 cases of PCLTCL and in 1 out of 8 cases of CBCL. C219 expression was found in 4 out of 10 cases of PCLTCL and in 2 out of 8 cases of CBCL. After chemotherapy both a higher staining intensity and a higher number of positive cells were found with MRPrl especially in patients with MF.The present study shows that lymphoid cells in both primary cutaneous lymphomas and benign skin disorders may express MDR related proteins and that the expression profile of these proteins is roughly related to the tumor cell phenotype. However, the functional role of these proteins in clinical drug resistance in primary cutaneous lymphomas has to be proven.

Multiple minute digitate hyperkeratoses (MMDH) is a relatively rarely described disorder of keratinization of unknown origin. We noticed that MMDH has been reported in the literature under a variety of synonyms. We observed two patients with MMDH and reviewed the literature. We concluded that MMDH is a skin disorder which can be properly separated from other disorders of keratinization and classified as a distinct entity. Two forms of MMDH exist: MMDH of early onset and MMDH of late onset. Both forms are described occurring in a widespread and in a localized pattern. The early onset form may be hereditary, the late onset form may present as part of a paraneoplastic syndrome.

Sézary syndrome (SS) is a rare cutaneous T-cell lymphoma. SS usually develops de novo. We describe a 23-year-old man with a proven history of severe atopic dermatitis since childhood, who developed SS. This case contributes to the discussion about the possibility of a relationship between inflammatory dermatitis, atopy and subsequent SS. We provide criteria that should be fulfilled to define such an association.

Granulomatous slack skin (GSS) is a rare cutaneous disorder characterized clinically by the evolution of circumscribed erythematous lax skin masses, especially in the body folds, and histologically by a granulomatous T-cell infiltrate and loss of elastic fibers. GSS is often associated with preceding or subsequent lymphoproliferative malignancies, especially mycosis fungoides (MF) and Hodgkin's disease (HD). No effective treatment is known yet. Whether this entity is a benign disorder, a peculiar host reaction to a malignant lymphoma, a precursor of malignant lymphoma or an indolent cutaneous T-cell lymphoma (CTCL) in itself is still a matter of debate.The results of the patients with GSS from the Netherlands are compared with the cases reported in the world literature.A female patient had had GSS for 8 years without developing a secondary malignancy. In a second female patient with a histologically confirmed diagnosis of MF, GSS developed 18 years later in the axillary and inguinal folds which had previously been affected by plaque-stage MF lesions. A third male patient with a 6-year history of erythematosquamous skin disease diagnosed as CTCL developed GSS. Moreover, granuloma formation was also found in a facial basal cell carcinoma, in a cervical lymph node and the spleen. Clonal rearrangements of the T-cell receptor beta genes were found in the 2 female patients; the male patient could not be tested.GSS is a rare clinicopathological entity. Only 34 patients have been described so far. The development of GSS within plaque MF lesions has not been reported before. Our third case developed very extensive skin lesions and showed a strong propensity to develop granulomas as compared to cases reported before. The presence of a clonal T-cell population was demonstrated in all cases tested. Our cases support the idea that GSS is a very rare and rather indolent type of CTCL. Apparently, the disease is associated with a peculiar immune response, characterized by granuloma formation and disappearance of elastic fibers resulting in the lax skin. The relationship between GSS and other preexisting or subsequent lymphoproliferative diseases (diagnosed in approximately 50% of the cases) warrants a life-long follow-up.

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-Sezary 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 Sezary 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.

Erythroderma may result from different causes. There have been no publications on this subject with special emphasis on survival.The aim of the study was to determine the cause of the erythroderma and the prognosis of these patients.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.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.Men with erythroderma, from causes other than Sézary syndrome, mycosis fungoides, or leukemia cutis, have a lower survival than men in the general population.

PURPOSE Primary cutaneous follicle center cell lymphomas (PCFCCL) are a distinct group of cutaneous B-cell lymphomas with a favorable prognosis after radiotherapy (RT) or polychemotherapy (PCT). In the literature, conflicting data exist regarding the efficacy and the relapse rate of both treatment modalities. In the present study, treatment results and follow-up data of a large group of PCFCCL are evaluated. PATIENTS AND METHODS Fifty-five patients with a PCFCCL who presented with skin lesions on either the head (n = 12), the trunk (n = 35), or lower legs (n = 8), and who were initially treated with RT (40 cases) or PCT (15 cases) were studied. RESULTS RT resulted in a complete remission in all 40 cases. Eight cases relapsed and three of these patients died as a result of their lymphoma. The estimated 5-year survival was 89%. Four of eight relapses and all three lymphoma-related deaths occurred in the group of patients presenting with tumor(s) on the lower legs. Treatment with cyclophosphamide, doxorubicin vincristine, and prednisone (CHOP) or cyclophosphomide, vincristine, and prednisone (COP) resulted in a complete remission in 14 of 15 cases. All four cases treated with COP relapsed, whereas only two of 11 patients treated with CHOP had a relapse. The estimated 5-year survival rate of the PCT group was 93%. CONCLUSION Both RT and CHOP PCT are highly effective modes of treatment for PCFCCL. In localized PCFCCL, RT is the treatment of choice. In patients with multiple tumors involving anatomic nonrelated parts of the skin, CHOP rather than COP PCT is the preferred mode of treatment. PCFCCL on the lower legs, a subgroup that characteristically occur in elderly patients, have a higher relapse rate and a less favorable prognosis than PCFCCL presenting on the head or trunk.

A 40-year-old woman who had been treated for mesangiocapillary glomerulonephritis by renal transplantation, and who still used furosemide, azathioprine, cyclosporine and prednisone, was admitted with multiple erythematous nodes on the lower legs. Pancreatogenic panniculitis caused by pancreatitis was diagnosed. The patient died with a haemorrhagic and necrotic pancreas one month after admission. Pancreatogenic panniculitis occurs in 2-3% of patients with pancreatitis or pancreatic carcinoma. It can be a first manifestation of an undetected pancreatic disease.

As the differential diagnosis of erythrodermic actinic reticuloid vs Sézary syndrome (SS) can be very difficult, we examined the value of the nuclear contour index (NCI) on blood lymphocytes as the criterion for differential diagnoses. The NCI is defined as the nuclear parameter divided by the square root of the nuclear area. Three different parameters were studied: mean NCI, percentage of cells with an NCI of 6.5 or greater, and the highest NCI. These indexes were studied on blood lymphocyte samples obtained from 10 patients with erythrodermic actinic reticuloid and were compared with the findings in 10 patients with other benign forms of erythroderma and in seven patients suffering from SS.The patients with erythrodermic actinic reticuloid differed significantly from the group with SS regarding the percentage of cells with an NCI of 6.5 or greater and the highest NCI, but not when the mean NCI was considered. All three parameters revealed nonsignificant results for erythrodermic actinic reticuloid compared with other benign forms of erythroderma. The group with SS differed significantly from the patients with other benign forms of erythroderma regarding all three parameters. By combining three morphometric criteria (mean NCI,or = 5.5;30% lymphoid cells with an NCI ofor = 6.5; and highest NCI,or = 11.5), all patients with erythrodermic actinic reticuloid or other benign forms of erythroderma and six of the seven patients with SS were correctly classified.Our data indicate that assessment of the NCI on peripheral blood lymphocytes is of value in the differential diagnosis of erythrodermic actinic reticuloid vs SS.

Actinic reticuloid (AR) is a severe photodermatosis occurring in elderly male patients. It is part of the spectrum of chronic actinic dermatitis (CAD) (Noms and Hawk, 1990). A diagnosis of AR should only be made when all the following three criteria are present: (i) either persistently infiltrated skin on light-exposed areas or generalized erythroderma; (ii) photosensitivity to a wide range of wavelengths, including UV-B, UV-A and part of the visible spectrum; and (iii) on histologic examination, a dermal infiltrate with presence of atypical lymphocytes.

Skin biopsy specimens from 15 patients with mycosis fungoides and Sezary syndrome, with simultaneously occurring plaques and tumours, were examined to assess phenotypic deviation. We focused on immunophenotypic differences between the two types of lesions with respect to the T-cell markers CD2, CD3, CD4, CD5 and CD8. In six patients (40%) loss of one or more T-cell markers occurred in at least one of the lesions. Three of the patients studied (20%) showed a difference in immunophenotype between plaques and tumours, with an additional loss of one of the T-cell markers in the tumours (respectively, CD5, CD2 and CD4). All three of these patients showed a larger number of blast cells in the tumour compared with the plaque. No correlation between this loss of antigenicity and the prognosis was observed. The results of this study show that different immunophenotypes can occur simultaneously in an individual patient. Furthermore, we were able to confirm a relationship between the number of intraepidermal CD1+ cells in plaque lesions and the prognosis.

Elastosis perforans serpiginosa (EPS) is an uncommon skin disease characterized by transepidermal elimination of abnormal elastic fibers. The disease is frequently associated with congenital connective tissue disorders or Down's syndrome. The pathogenesis of EPS is still unclear. There are a few reports in the literature about a familial occurrence of EPS in which different modes of inheritance are suggested. To support the hypothesis of a congenital origin of the disease, we have studied another family with EPS.In this study, we describe a family in which two sisters and a brother were affected by EPS. The father and three paternal uncles were most probably affected by the same disease. There were no signs of other congenital connective tissue disease in the family members.An autosomal dominant mode of inheritance with variable expression of EPS is suggested.

A 19-year-old female with ectodermal dysplasia, lipoatrophy, diabetes mellitus, and amastia is described. This complex of symptoms is very similar to that of a case published by Pinheiro et al [1983] under the acronym of AREDYLD syndrome.

We report on a 2-year-old male patient with a Spitz naevus on the left lower leg. In addition to the characteristic histological features of a Spitz naevus, a balloon cell component was found.