Immunofluorescence and immunoelectron microscopy analyses of a human monoclonal anti-epithelial cell surface antibody that recognizes a 185-kD polypeptide: a component of the paraneoplastic pemphigus antigen complex?

We recently reported the production of a human monoclonal antibody (MoAb) derived from a patient with pemphigus vulgaris (PV) that binds to the keratinocyte membrane and reacts with a 185-kD polypeptide by immunoblot analysis. We have since examined the tissue specificity of that MoAb, F12. By indirect immunofluorescence (IIF), F12 stained both the cell membrane and the basement membrane zone of stratified squamous epithelia. Moreover, MoAb F12 stained other epithelial tissues, such as urinary bladder, small bowel, thymus, and liver, and non-epithelial tissues, such as myocardium. Indirect immunoelectron microscopy (IIEM) analysis showed that MoAb F12 bound to a component common to desmosomal and hemidesmosomal plaques and to zona adherens-type junctions between hepatocytes and bile duct cells. Inhibition experiments were then performed with sera from patients with pemphigus vulgaris, pemphigus foliaceus, paraneoplastic pemphigus, or bullous pemphigoid. Three sera blocked F12 reactivity; two were from paraneoplastic pemphigus patients and the other was from the pemphigus vulgaris patient whose peripheral blood lymphocytes were used to make F12. All these sera recognized a 185-kD band that co-migrated with the polypeptide labeled by MoAb F12 on immunoblots. In addition, the IIF and IIEM staining patterns of MoAb F12 were similar to those observed with sera from two patients with paraneoplastic pemphigus. These observations suggest a relationship between MoAb F12 and the autoimmune response characterizing paraneoplastic pemphigus patients' sera.

Identification of a new antibody population directed against a desmosomal plaque antigen in pemphigus vulgaris and pemphigus foliaceus.

Pemphigus vulgaris and pemphigus foliaceus are characterized by autoantibodies directed against transmembrane glycoproteins of desmosomes. F12, a human monoclonal autoantibody that binds to the desmosomal plaque, recognizes a 180-190-kDa doublet when immunoblotted against bovine tongue epithelium. Because F12 was derived from the peripheral blood lymphocytes of a patient with pemphigus vulgaris, we looked for the presence of anti-180-190-kDa antibodies in pemphigus vulgaris and pemphigus foliaceus serum. By immunoblot analysis, a third of the pemphigus serum contained anti-180-190-kDa antibodies that belonged to IgG subclass 1 or 3, unlike those that recognized desmogleins 1 and 3 (IgG4). By immunoelectron microscopy analysis on human oral mucosa and human skin with mAb to human IgG3, pemphigus serum containing anti-180-190 kDa antibodies recognized desmosomal plaques. The presence of antibodies with F12 properties in pemphigus serum was further demonstrated by a rabbit anti-F12 idiotype antiserum that allowed detection of F12 idiotype in serum with anti-180-190-kDa antibodies. These results indicate that some pemphigus vulgaris and pemphigus foliaceus serums contain antibodies that react with both intra- and extracellular structures of desmosomes and further demonstrate the heterogeneity of the autoimmune response in both types of pemphigus.

Overlapping distribution of autoantibody specificities in paraneoplastic pemphigus and pemphigus vulgaris.

Paraneoplastic pemphigus is an autoimmune bullous skin disease in which autoantibodies immunoprecipitate a characteristic antigenic complex. The objective of this study was to analyze by immunoblotting and immunoelectron microscopy the autoimmune response in five patients with clinical and immunohistologic features typical of paraneoplastic pemphigus. In a first series of experiments, immunoblotting and immunoelectron microscopy were performed using anti-human whole Ig. Although immunoblotting results were consistent with the autoantibody specificities previously described in paraneoplastic pemphigus sera, immunoelectron microscopy demonstrated the presence of Ig deposits on desmosomal plaques, on hemidesmosomes and, surprisingly, on both the extracellular part of desmosomes and the keratinocyte plasma membrane. In a second series of experiments, immunoblotting and immunoelectron microscopy were carried out using antihuman IgG subclasses. The major observation was that two sera contained, in addition to the anti-desmoplakins I-II, anti-185-kD and anti-230-kD autoantibodies, autoantibodies that stained the desmoglea by indirect immunoelectron microscopy and bound to a 130-kD polypeptide by immunoblotting. One serum was particularly demonstrative: IgG1 bound to the 250- and 220-kD bands corresponding to desmoplakins I and II on immunoblots and to the desmosomal plaques of keratinocytes in immunoelectron microscopic preparations; IgG3 recognized a 185-kD immunoblotting band and hemidesmosomes and desmosomal plaques by immunoelectron microscopy; IgG4 bound to the 130-kD immunoblotting band of pemphigus vulgaris and labeled the desmoglea and the keratinocyte plasma membrane by immunoelectron microscopy. These results demonstrate that the paraneoplastic-pemphigus autoimmune response involves both intracellular and extracellular desmosomal antigens and suggest an overlapping distribution of autoantibody specificities among autoimmune bullous skin diseases.

CD4+ CD56+ cutaneous neoplasms: a distinct hematological entity? Groupe Français d'Etude des Lymphomes Cutanés (GFELC).

We report seven cases of particular cutaneous tumors selected from the register of the French Study Group on Cutaneous Lymphomas. The patients (three men, four women) were aged 37-86 years. They initially presented with cutaneous nodules or papules. Three cases presented with regional lymph nodes. Stagings were negative, except for one patient with bone marrow involvement. Histological features were relevant with pleomorphic medium T-cell lymphoma, but these cells exhibited a distinguishing phenotype. They were positive for CD4, CD56, and also CD45, CD43, and HLA-DR. All other T-cell and B-cell markers were negative. The myelomonocytic markers (CD13, CD14, CD15, CD33, CD117, myeloperoxidase, and lysozyme) were negative excepted CD68, which was clearly positive in four cases and weakly in two cases. Others natural killer cell markers (CD16, CD57, TiA1, granzyme B), TdT, and CD34 were negative. Polymerase chain reaction studies did not detect any B or T clonal rearrangement. The cytogenetic studies, performed in five cases, showed a del(5q) in two cases. All patients were treated successfully by polychemotherapy, but relapsed quickly in the skin, between 4 and 28 months. Five patients developed bone marrow involvement, with leukemia in three cases, and they died in 5-27 months. One patient died at 17 months with skin progression. The seventh patient is alive at 33 months, with cutaneous progression. The origin of these cells is unclear. Despite expression of CD4 or CD56, we failed to demonstrate a T-cell, natural killer cell origin. However, CD4 and CD56 are not specific for T or natural killer lineages. Although these two markers are also known to be expressed by monocytic cells, classic myeloid antigens were negative. These seven cases, together with other rare similar cases already reported, seem to represent a distinct entity likely developed from hematological precursor cells.

Relationship between the in vivo localization and the immunoblotting pattern of anti-basement membrane zone antibodies in patients with bullous pemphigoid.

OBJECTIVE: To compare the localization of anti-basement membrane zone (BMZ) antibodies bound in vivo with the antigenic specificities of circulating anti-BMZ antibodies in patients with bullous pemphigoid (BP). DESIGN: Comparison of the results of an examination of the skin specimens of the patients using direct immunoelectron microscopy and direct immunofluorescence on 1-mol/L sodium chloride-split skin with the results of an analysis of the corresponding serum samples using the immunoblot technique. SETTING: Immunodermatology department in a teaching hospital. PATIENTS: Thirty-six patients with typical BP and circulating anti-BMZ antibodies. RESULTS: Serum samples from 22 patients with BP indicated only BP antigen 1 in the results of immunoblot analysis. Using direct immunofluorescence, an analysis of the peribullous skin samples obtained from these 22 patients showed deposits of IgG exclusively located along the epidermal side of sodium chloride-split skin; the results of direct immunoelectron microscopic examination showed deposits of IgG located on the intracellular portion of hemidesmosomes in 18 (82%) of these 22 specimens, whereas 4 biopsy specimens had linear IgG deposits located both intracellularly and extracellularly along the keratinocyte plasma membrane. The results of immunoblot analysis of the serum samples from 5 patients with BP indicated BP antigen 2 alone; the results of direct immunoelectron microscopic examination of peribullous skin samples from these 5 patients showed linear intracellular and extracellular deposits along the keratinocyte membrane, corresponding to an epidermal fluorescence labeling pattern of peribullous sodium chloride-split skin in 2 patients and a combined (dermal and epidermal) pattern in 3 patients. CONCLUSION: The 2 different patterns of reactivity of anti-BMZ antibody deposits bound in vivo closely corresponded to the antigenic specificities indicated in the corresponding serum samples of the patients. These results are in accordance with those previously obtained in vitro and argue for identical binding profiles of circulating antibodies that are bound in vivo in BP.

Polymerase chain reaction analysis of immunoglobulin gene rearrangement in cutaneous lymphoid hyperplasias. French Study Group for Cutaneous Lymphomas.

UNLABELLED: The differential diagnosis of cutaneous lymphoid hyperplasia and B-cell lymphoma may be difficult. Whether the detection of clonal immunoglobulin gene rearrangement in the cutaneous lesion is predictive of a malignant outcome remains controversial. We therefore studied cases of cutaneous lymphoid hyperplasia by polymerase chain reaction analysis. DESIGN: Retrospective study of patients seen between 1988 and 1996. SETTING: Two dermatology university departments. PATIENTS: Twenty-four patients with cutaneous lymphoid hyperplasias were included according to clinical, histopathological, and immunophenotypic criteria. MAIN OUTCOME MEASURES: Clinical, histopathological, and laboratory findings. RESULTS: There were 13 men and 11 women (mean age, 49 years) who presented with erythematous or violaceous papules or nodules. The lesions were unique in 13 cases and multiple in 11 cases. All patients had immunochemical evidence of a mixed T- and B-cell infiltrate with polytypic B cells. Polyclonality was demonstrated in 23 patients, whereas a dominant B-cell clone was detected in 1 patient. No lymphoma developed during the follow-up (median, 4 years). In the same period, we studied 53 cases of B-cell lymphomas. Thirty-five (66%) of the 53 cases had a detectable clonal immunoglobulin gene rearrangement. CONCLUSIONS: In the majority of our cases, polyclonality demonstrated by polymerase chain reaction analysis was in accordance with the diagnosis of cutaneous lymphoid hyperplasia. In 1 of the 24 patients, the presence of a B-cell clone could be evidenced. This fact did not modify the treatment as there were no histological or immunophenotypic signs suggestive of a lymphoma.

Evaluation of clinical criteria for diagnosis of bullous pemphigoid. French Bullous Study Group.

OBJECTIVE: To check the potential usefulness of clinical criteria for the diagnosis of bullous pemphigoid when state-of-the-art techniques such as Western immunoblotting, immunoprecipitation, and indirect immunofluorescence on salt-split skin or direct immunoelectron microscopy are not available. DESIGN: Comparison of the clinical criteria between 2 groups (with and without bullous pemphigoid) as defined by immunoelectron microscopy used as standard criterion, in a prospective study. Multivariate logistic regression analysis was carried out by including all items that were statistically significant (at P < .05 level) in univariate analysis. SETTING: Five dermatology departments in teaching hospitals. PATIENTS: The 231 patients studied had subepidermal autoimmune bullous diseases with linear IgG or C3 deposits in the basement membrane zone (157 with bullous pemphigoid, 33 with cicatricial pemphigoid, 30 with epidermolysis bullous acquisita, 5 with lupus erythematosus, and 6 others). A second set of patients was used to calculate predictive values. RESULTS: The multivariate logistic stepwise analysis resulted in a final set of predictors that included only 4 items: absence of atrophic scars, absence of head and neck involvement, absence of mucosal involvement, and age greater than 70 years. No additional variables met the .05 significance level to enter into the model. If 3 of these 4 characteristics were present, a diagnosis of bullous pemphigoid could be made with a sensitivity of 90% and a specificity of 83%; these predictive values were calculated on a sample of 70 new cases. CONCLUSIONS: With and estimated incidence of bullous pemphigoid among subepidermal autoimmune bullous diseases of 80%, the presence of 3 of the 4 significant criteria allows the diagnosis of bullous pemphigoid, with a positive predictive value of 95%. Our set of clinical criteria thus allows the diagnosis of bullous pemphigoid with good validity for both clinical practice and therapeutic trials.

Differences in Epstein-Barr virus expression between primary and secondary cutaneous angiocentric lymphomas. French Study Group of Cutaneous Lymphomas.

BACKGROUND: Epstein-Barr virus (EBV) has been demonstrated in angiocentric immunoproliferative lesions, suggesting that it could be a causative factor. We investigated for the presence of EBV in 12 primary and 2 secondary cutaneous angiocentric lymphomas (CALs). OBSERVATIONS: In the 2 secondary CALs, strong reactivity for EBV RNAs and latent membrane protein 1 were detected on paraffin-embedded sections. In contrast, 10 of 12 primary CALs were completely negative for EBV RNAs and latent membrane protein 1. In 2 primary CALs, EBV RNAs and latent membrane protein 1 were detected in few tumor cells. In the group of primary CALs, 8 of 12 were still alive at last follow-up, 3 died of systemic lymphoma, and 1 died of another cause, whereas both patients with secondary CALs died of disease within 1 year. CONCLUSION: Differences in the presence of EBV and clinical behavior between primary and secondary CALs suggest that different mechanisms are operative in the pathogenesis of these conditions, and indicate that the 2 groups should be considered separately.

A prospective study of cutaneous intolerance to topical mechlorethamine therapy in patients with cutaneous T-cell lymphomas. French Study Group of Cutaneous Lymphomas.

OBJECTIVE: To study the exact frequency and the histological features of cutaneous intolerance to mechlorethamine (CIM) hydrochloride therapy in patients with cutaneous T-cell lymphomas, including Langerhans cell histiocytosis. DESIGN: A multicenter prospective study was conducted from January 1, 1994, to May 31, 1996, in 12 different hospitals in France. PATIENTS: Of the 52 patients with cutaneous T-cell lymphomas or Langerhans cell histiocytosis, 35 were men and 17 were women, aged 18 to 87 years. Of the 52 patients, 35 had mycosis fungoides, 8 had nonepidermotropic cutaneous lymphoma, 7 had lymphomatoid papulosis, 1 had Sézary syndrome, and 1 had Langerhans cell histiocytosis. METHODS: Patients were treated with topical applications of a 0.02% aqueous solution of mechlorethamine. The diagnosis of CIM was determined by the presence of erythema and pruritus. Patients who developed CIM underwent closed patch testing with three 10-fold dilutions of 0.02% mechlorethamine solution. A positive patch test result was the presence of erythema and pruritus, a weak result was the presence of simple erythema without pruritus, and a negative result was the absence of erythema and pruritus. Skin biopsy specimens from patients with positive patch test results were obtained in patients who developed CIM. The biopsy specimens were reviewed, and the results determined by 2 pathologists (E.T. and J.W.). The histopathological findings were classified in 3 categories: (1) spongiotic dermatitis, (2) irritant dermatitis, and (3) insignificant or normal. In September 1998, the referring physicians were contacted if mechlorethamine therapy had been continued in patients with CIM. RESULTS: Of the 52 patients, 43 were evaluated for tolerance to mechlorethamine therapy. Of the 43 patients, CIM developed in 23, from 4 days to 9 months after the initiation of mechlorethamine therapy. Of those 23 patients, CIM developed within 3 months in 21 and within 1 month in 13. Closed patch tests were performed in 21 of the 23 patients who developed CIM. The results of the patch test were positive in 12, weak in 4, and negative in 5. Of these 21 patients, 14 skin biopsy specimens were obtained in 14 different patients who had positive or weak patch test results. The specimens showed histological features that were consistent with spongiotic dermatitis in 9 patients, irritant dermatitis in 2, and insignificant or normal in 3. All 9 patients with histological features of spongiotic dermatitis discontinued mechlorethamine therapy. All 5 patients without histological features of spongiotic dermatitis were able to resume mechlorethamine therapy. These results do not correlate with those of previous study results. CONCLUSIONS: Mechlorethamine therapy is a cost-effective and easily administered treatment for cutaneous T-cell lymphomas. Our study shows that allergic dermatitis caused by mechlorethamine therapy is an early and frequent adverse reaction in patients with cutaneous T-cell lymphomas. The most common histological feature of patients with CIM is spongiotic dermatitis.

Binding of autoantibodies is not restricted to desmosomes in pemphigus vulgaris: comparison of 14 cases of pemphigus vulgaris and 10 cases of pemphigus foliaceus studied by western immunoblot and immunoelectron microscopy.

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune blistering diseases characterized by a loss of cell-cell adhesion and by autoantibodies directed against epidermal cadherins. PF antigen has been established as desmoglein I which is located strictly on the desmosome, whereas the precise ultrastructural localization of PV antigen remains unclear and controversial to date. To further investigate this question, we compared the location of immune deposits in 14 patients with PV and 10 patients with PF by both direct and indirect immunoelectron microscopy (IEM). Inclusion criteria were based upon clinical features, histological level of cleavage and characterization of circulating antibodies by Western blot on epithelial bovine tongue extracts. IEM was performed on unfixed 0.7-mm slices of skin for the direct technique or on normal skin for the indirect technique using peroxidase labelling. In PF, by both direct and indirect IEM, immune deposits were located on the extracellular part of desmosomes (desmoglea) in all the samples studied. In PV, by both direct and indirect IEM, deposits were situated on the desmoglea and along large portions of the keratinocyte membrane without desmosomal structures in 15 of the 18 samples studied and only on the desmoglea in 3 samples. These results suggest that, in contrast to PF, the target antigen in PV is not always restricted to desmosomes. As various types of adherens junctions have been reported to mediate cell adhesion in the epidermis, the PV antigen could be a component of desmosomes and of other focal adhesions.

VP-16, cisplatin, doxorubicin, and bleomycin in metastatic Merkel cell carcinoma. Report of a case with long-term remission.

A complete response with combination chemotherapy was obtained in a patient with metastatic Merkel cell carcinoma. This complete response lasted 15 months. This case report demonstrates the chemosensitivity of this metastatic disease when treated with combination chemotherapy.

[Childhood acromelalgia a propos of a case revealing Fabry's disease]. / Acromélalgies de l'enfant a propos d'une observation révélatrice de maladie de Fabry.

The occurrence of an acrosyndrome (Raynaud's phenomenon, erythermalgia, acrodynia...) in childhood may be the first manifestation of a general disease. Though it can be an early onset Raynaud's disease, it could also be the first sign of a connective tissue disease (juvenile polyarthritis, mixed connectivitis...) or of a overload disorder. We report a case of childhood-onset acromelalgia leading to the discovery of Fabry's disease. This chromosome X-linked hereditary disorder, resulting in the ubiquitous accumulation of neutral sphingolipids, is usually rapidly suspected by the finding of "boxer-short" angiokeratoma. Diagnosis is confirmed by the ophthalmic examination (cornea verticillata), by the pathological examination of a skin sample, and by the measure of alpha-galactosidase A activity. Treatment is usually only symptomatic, but the discovery of the mutations responsible for the disease could open the way to specific therapy.

[Comparative study of HMB-45 monoclonal antibody uptake on various benign and malignant melanocytic lesions]. / Etude comparative de la fixation de l'anticorps monoclonal HMB-45 sur diverses lésions mélanocytaires bénignes et malignes.

In order to evaluate a possible discriminatory diagnosis interest of HMB-45 monoclonal antibody in different melanocytic population, it was tested on 48 benign and malignant melanocytic lesions embedded in paraffin. There were made of 16 benign nevus (33%), 18 dysplastic nevus (38%) and 14 malignant melanomas (29%). The reaction was positive in 11 benign tumors (69%), 18 dysplastic nevus (100%), and 12 malignant melanomas (86%); negative in 5 dermal nevus (31%) and 2 desmoplastic melanomas (14%). We have researched, by the KHI square (chi 2) statistical test, a relation between the reaction intensity, its cutaneous location, and the tumor type. The reaction intensity is not statistically linked with the tumor type. The cutaneous location of the reaction is statistically more heterogeneous in malignant melanoma than in benign or dysplastic melanocytic lesions. Among the dysplastic nevus, 6 cases (38%), of the familial type, have an heterogeneous reaction looking like the malignant melanoma's one. However, there is no significant difference, in the reaction pattern, between dysplastic and benign lesions. Nevertheless some dysplastic nevus seems to have a phenotypic expression for HMB-45 midway between benign and malignant melanocytic lesion, that will be interesting to precise. Otherwise, the simple use and the staining of HMB-45 monoclonal antibody are of great interest to assess the depth of primary cutaneous melanoma and to diagnose secondary melanoma. However, the negativity of the spindle cell type justify the association of other markers, particularly the S100 protein, which is more sensitive, in the diagnosis of desmoplastic malignant melanoma.

[Benign glandular schwannoma and Recklinghausen disease. Report of a case]. / Schwannome glandulaire bénin et maladie de Recklinghausen. A propos d'un cas.

The authors describe the case of a 32 year-old woman with a congenital neurofibromatosis referred for excision of a painful subcutaneous nodule of the left popliteal space. The histological study showed a tumor displaying a biphasic pattern made of fascicles of benign spindle cells admixed with mucinous epithelium. Immunohistochemistry (cytokeratin X, ECA X) and electron microscopy helped to prove the true epithelial nature of the glandular components. Glandular schwannoma has rarely been described, especially in a benign histological pattern; this one has never been reported in association with Von Recklinghausen's disease. The histogenesis of the glandular schwannoma remains uncertain.

[Syringomatous carcinoma a propos of three cases with a review of the literature]. / Le carcinome syringomateux à propos de trois observations avec revue de la littérature.

Three cases of syringomatous carcinoma are reported. It is a rare adnexal neoplasm of the skin with a marked propensity for early infiltrative and locally aggressive growth. The tumor usually involves the face and particularly the upper lip. Microscopically, this tumor is characterized by syringomatous pattern and sclerotic collagenous stroma.

[Evaluation of histological criteria for bullous pemphigoid. Correlation with antigens recognized by immunoblotting of anti-epidermal autoantibodies]. / Evaluation des critères histologiques de pemphigoïde bulleuse. Relation avec les antigènes reconnus en immunotransfert par les auto-anticorps anti-épiderme.

The aim of this study was to evaluate the histological findings observed in patients with bullous pemphigoid in whom the diagnosis of bullous pemphigoid could be confirmed by direct immunofluorescence and immunoblot serum analysis. Seven histological criteria were considered for selection of skin biopsy specimens: 1) cleavage of dermal epidermal junction; 2) migration of eosinophils along dermal epidermal junction; 3) presence of intra epidermal eosinophils (with or without associated spongiosis); 4) absence of keratinocyte necrosis; 5) absence of acantholysis; 6) absence of dermal fibrosis; 7) absence of vasculitis. Depending on the number of criteria observed the histological picture was considered as: highly suggestive, suggestive or poorly suggestive of bullous pemphigoid. The histological picture was considered as highly suggestive in 50% of cases, suggestive or poorly suggestive in 37% and 13% of cases respectively. Migration of eosinophils along dermal epidermal junction was observed in 23 biopsy specimens (50%). Histological findings considered as poorly suggestive of bullous pemphigoid consisted of a prurigo-like or an eczematous-like or a drug induced-like picture or no specific cutaneous erosions. An histological picture highly suggestive of bullous pemphigoid was observed in 67% of patients whose serum contained anti-BPAG2 antibodies and in only 36% patients of without anti-BPAG2 antibodies (p=0,04). On the contrary, only one bullous pemphigoid patient (4%) with circulating anti-BPAG2 antibodies had a histological picture poorly suggestive of bullous pemphigoid. These findings are in accordance with the pathogenic properties of anti-BPAG2 antibodies demonstrated in animal models. This study showed that: 1) typical histological findings of bullous pemphigoid are only observed in 50% of skin biopsy specimens. 2) The diagnosis of bullous pemphigoid should be considered in elderly patients even when a poorly specific prurigo-like or eczematous-like histological picture is observed. Moreover, it underlines the usefulness of direct immunofluorescence of skin biopsy specimens and indirect immunofluorescence and immunoblot analysis of serum in such atypical cases of bullous pemphigoid.

[Epidermal nevus associated with a type I neurofibromatosis and a nephroblastoma: a new epidermal nevus syndrome?]. / Association d'un naevus épidermique, d'une neurofibromatose de type I et d'un néphroblastome: un nouveau syndrome du naevus épidermique?

We report the case of a 6-year-old boy who showed a large epidermal nevus mixed with a plexiform neurofibroma, which was associated with "café au lait" macules and a nephroblastoma. This association could not be classified in one of the five well defined epidermal nevus syndrome. To our knowledge this is the first time that this type of epidermal nevus syndrome has been described, which raises the question of the relationship between neurofibromatosis 1, nephroblastoma and epidermal nevus.

[Langerhans-cell histiocytosis in twin sisters]. / Histiocytose langerhansienne chez deux soeurs jumelles.

BACKGROUND--Histiocytosis of Langerhans cells includes a range of clinical manifestations that have been described as bone eosinophilic granuloma, Hand-Schüller-Christian syndrome, Letterer-Siwe syndrome and Hashimoto-Pritzker histiocytosis. These syndromes represent a spectrum of severity and prognosis of the same underlying disorder which is usually sporadic. It has occurred in monozygotic twins and in a familial pattern. This report describes monozygotic twins who developed the disease a few months after their father was found to be suffering from Hodgkin's disease. Case n. 1.--A 4 month-old girl was admitted because of fever, disseminated lymphadenopathy and hepatomegaly. She also had interstitial pneumonia. Infiltrating abnormal histiocytes were demonstrated in lymph node and bone marrow biopsies. X-rays showed lytic areas in the skull. Serology for EBV infection was negative. Special studies with immune markers of lymph node histiocytes confirmed the diagnosis of Langerhans cell histiocytosis, and more precisely, Letterer-Siwe syndrome. The patient was given prednisolone followed by vinblastine without success. She was given etoposide 11 weeks later, which induced remission. This treatment was replaced by vinblastine when the patient was aged 2 years 9 months. Case n. 2.--The monozygotic twin of the case n. 1 was also admitted at 4 months of age because of the same manifestations. Laboratory findings were identical to those of her sister, as was her response to the same drugs. The father was diagnosed as having Hodgkin's disease 3 months before the first manifestation of Langerhans cell histiocytosis in his daughters. His maternal uncle had also been treated for Hodgkin's disease. Immunologic studies of the twin were negative. CONCLUSION--These cases of Langerhans cell histiocytosis in monozygotic twins have no apparent relationship with the Hodgkin's disease of their father. Etoposide seems to be useful for treating such severe forms of the disease.

[Osteoarticular manifestations of pustulosis palmaris et plantaris]. / Les manifestations ostéo-articulaires de la pustulose palmo-plantaire.

In 6 patients with clinically and histologically proven pustulosis palmaris et plantaris the disease was complicated by osteo-articular manifestations. Five patients presented with articular symptoms and one with aseptic subacute osteomyelitis. The distribution of these bone and joint disorders was different from that of Sonozaki's "pustulotic arthro-osteitis": in contrast with the latter, the anterior chest was inconstantly involved whereas the spine, sacro-iliac joints and peripheral articulations were more frequently affected. Although the B27 antigen is usually absent, it seems possible to classify the rheumatic disorders of pustulosis palmaris et plantaris among seronegative spondylo-arthropathies.

[Spontaneous rupture of subclavian artery disclosing Ehlers-Danlos disease. A case]. / Rupture spontanée d'artère sous-clavière révélant une maladie d'Ehlers-Danlos. Une observation.

The authors report the case of a 30-year old man who suffered spontaneous rupture of the right subclavian artery. Treatment consisted of carotid-axillary graft since the fragility of the vessel precluded direct suture. The clinical symptoms, together with histological and ultrastructural examinations led to a diagnosis of Ehlers-Danlos syndrome with purely arterial manifestations.