Schnitzler's syndrome: diagnosis, treatment, and follow-up.

Schnitzler's syndrome is characterized by recurrent urticarial rash and monoclonal gammopathy, associated with clinical and biological signs of inflammation and a long-term risk of AA amyloidosis and overt lymphoproliferation. An extensive literature review was performed, and the following questions were addressed during an expert meeting: In whom should Schnitzler's syndrome be suspected? How should the diagnosis of Schnitzler's syndrome be established? How should a patient with Schnitzler's syndrome be treated? How should a patient with Schnitzler's syndrome be followed up?. A diagnosis of Schnitzler's syndrome is considered definite in any patient with two obligate criteria: a recurrent urticarial rash and a monoclonal IgM gammopathy, and two of the following minor criteria: recurrent fever, objective signs of abnormal bone remodeling, elevated CRP level or leukocytosis, and a neutrophilic infiltrate on skin biopsy. It is considered probable, if only 1 minor criterion is present. In patients with monoclonal IgG gammopathies, diagnosis is definite if three minor criteria are present and possible if two are present. First-line treatment in patients with significant alteration of quality of life or persistent elevation of markers of inflammation should be anakinra. Follow-up should include clinical evaluation, CBC and CRP every 3 months and MGUS as usually recommended.

[Schnitzler syndrome and Waldenström disease. Fatal outcome of the original case]. / Syndrome de Schnitzler et maladie de Waldenström. Evolution terminale du cas princeps.

The association between chronic urticaria, macroglobulinaemia and various other manifestations has been individualized as Schnitzler's syndrome. We report the terminal course of an original case followed up for 20 years, which ended as lymphoplasmocytic lymphoma with multiple sites, whereas no lymphomatous proliferation, meticulously looked for, had never been found hitherto. The lymphoma, associated with a macroglobulinaemia level above 5 milligrams, was diagnosed as Waldenström disease. Although most cases of Schnitzler's syndrome seem to follow a benign course (but the follow-up is not always long) a few cases have been reported showing evolution towards, or association with, lymphoma. This indicates that the follow-up of patients with Schnitzler's syndrome should be prolonged.

[Pseudotumoral lupus anetoderma. Child chorea. Development over 28 years]. / Anétodermie lupique pseudo-tumorale. Chorée infantile. Evolution sur 28 ans.

The finding in a 40-year old and apparently healthy woman of a pseudotumoral lesion of the left arm which had gradually developed over a 9-year period led to a tentative clinical diagnosis of lupus anetoderma. This diagnosis was confirmed on the one hand by histological examination of the skin--which showed almost total disappearance of dermal elastic fibres, while the lympho-histiocytic infiltrate was so discreet that it excluded a deep lupus--and on the other hand by direct immunofluorescence, with lupus band on the lesion and a few abnormalities of the exposed and covered healthy skin. A history of chorea at the age of 13 years raised the problem of a possible relationship between this neurological disease and a systemic lupus erythematosus. This hypothesis was supported by resolutive episodes of arthralgia and abnormal laboratory findings, such as accelerated ESR, leucopenia, decrease of complement and presence of homogeneous antinuclear antibodies. Anticardiolipin antibodies, circulating anticoagulants and VDRL test were negative. Treatment with anti-malarials brought about some degree of cutaneous shrinkage and a significant decrease in ESR. This case is reported because anetoderma as sole manifestation of systemic lupus erythematosus and the occurrence, 17 years previously, of chorea are exceptional events.

[Retinoids and the prevention of cutaneous epitheliomas: 1977-1987]. / Rétinoïdes et prévention des épithéliomas cutanés: 1977-1987.

In 1977 we undertook a prospective study aimed at evaluating the preventive effects of a retinoid (etretinate, Roche) on the occurrence of skin carcinomas in dermatoses carrying a high risk of malignancy. Ten patients were included in the study: 4 had Xeroderma pigmentosum (XP), 4 had basal cell naevus syndrome (BCN), and there was 1 case each of porokeratosis of Mibelli (PM) and familial epitheliomatosis of Ferguson-Smith (EFS). All recorded carcinomas had been cured before treatment was initiated. The number of epitheliomas which developed during treatment with etretinate was compared with the number of epitheliomas recorded during the months or years preceding this treatment or during trial periods without treatment. The results obtained were very encouraging: 1. In patients with XP the actinic keratosis rapidly regressed, and the dryness of the skin was markedly reduced during the 5 years under etretinate. During the period without etretinate skin dryness and multiple actinic keratosis soon reappeared, as did, in one case, numerous basal cell carcinomas (BCC). However, etretinate did not prevent the occurrence of a malignant melanoma and of a few lesions of lentigo and naevus. 2. In the first case of BCN concerning two sisters, one treated the other untreated, less BCC lesions and, mainly, less BCN lesions were recorded in the sister treated than in the untreated sister. In the second case of BCN 28 BCC lesions developed while the patient was under observation without any treatment during 6 months, whereas only 31 BCC lesions had been recorded during 6 years under etretinate.(ABSTRACT TRUNCATED AT 250 WORDS)

[Multiple tumors of the follicular infundibulum with basocellular degeneration. Apropos of a case]. / Tumeurs multiples de l'infundibulum pilaire avec dégénérescence baso-cellulaire. A propos d'un cas.

A progressive papular eruption on the face, limbs and vulva had been present for seven years in a 38-year old female patient. Some papules were small and confluent while others were sparse, as in nodular prurigo. Histology showed massive proliferation of the follicular sheath epithelium, connected to the lower surface of the epidermis. The lesion formed a plate-like area very similar to that observed in superficial basal cell carcinoma and corresponding to a tumour of the follicular infundibulum. Remarkable features of this case were the large number of lesions, their photosensitivity (they became pruriginous and increased in size after exposure to the sun), the presence of eccrine sweat glands beneath a skin lesion of the thigh, the basal cell degeneration of two lesions and the slight improvement observed after etretinate therapy. To our knowledge, such findings have not yet been reported in tumours of the follicular infundibulum.

Radiation induced formation of giant cells (Saccharomyces uvarum). I. Budding process and chitin ring formation.

X-irradiated yeast cells (Saccharomyces uvarum) grown in liquid media stop mitosis and form giant cells. Chitin ring formation, being a prerequisite for cell separation, was studied by fluorescence microscopy using calcofluor white, a chitin specific dye. Experiments with inhibitors of DNA synthesis (hydroxyurea) and chitin synthesis (polyoxin D) demonstrate chitin ring formation to be dependent on DNA synthesis, whereas bud formation is independent of DNA synthesis and chitin ring formation respectively. Basing on these results the formation of X-ray induced giant cells implies one DNA replication which in turn induces the formation of only one chitin ring between mother cell and giant bud. Obviously no septum can be formed. Thus cell separation does not occur, but the bud already formed, produces another bud demonstrating that bud formation itself is independent of DNA synthesis.

[Cutaneous responses to an injectable collagen implant (zyderm). Clinical, histological and ultrastructural correlations after intradermal tests]. / Réponses cutanées à l'implant de collagéne injectable (zyderm). Corrélations cliniques, histologiques et ultrastructurales aprés tests intradermiques.

A test implant of Zyderm collagen was carried out on 250 patients using the volar forearm site. The behaviour of the implant in the host tissue was followed-up in 6 cases by both direct and electron microscopy. There were 14 positive reactions. Biopsy was carried out in 3 cases, all of which exhibited severe reactions; foreign body granulomata were found in 2 of these, perivascular lymphocytic infiltration in the third. All 3 had a follow-up for 3 months and the biopsy sites healed normally. Trial implants are always advisable with collagen material. In order to avoid the possibility of such delayed hypersensitivity reactions, the test implant should be investigated at 72 hours and kept under observation for 4 weeks prior to carrying out the full corrective procedure. In two cases, reactive adverse reactions at the collagen implant treatment site were observed in spite of negative reaction at the test site. Nevertheless evidence suggests that Zyderm injectable collagen is a suitable material, leading to good cosmetic results; it carries minimal risk and is well tolerated even after a long period of time.

[Diagnostic value of electron microscopy in dermatology]. / Intérêt diagnostique de la microscopie électronique en dermatologie.

Basing themselves on their personal experience, the authors stress the main indications and the value of electron microscopy in dermatology. In some cases it provides an indispensable adjunct to standard light microscopy (tumor pathology, cutaneous lymphoma, collagenosis, storage diseases, etc). In other cases, it provides greater insight into dermatological affections, such as pigmentation disorders or bullae. Ultrastructural studies should therefore often be included in a thorough morphological examination of a skin biopsy.

[Keratosis lichenoides chronica with mucous membrane involvement and ocular pseudo-pemphigus. Follow-up study over 18 years. Retinoid therapy (author's transl)]. / Kératose lichénoïde chronique avec atteinte muqueuse synéchiante sévère. Etude évolutive sur 18 ans. Thérapeutique par le rétinoíde aromatique.

A very uncommon ocular and mucocutaneous syndrome is reported. Cutaneous manifestations include keratotic plugs occasionally disposed into verrucous plaques (in mountainous chain), lichenoid lesions on face, neck and hand's back, and nail's involvement. Histologically three types of lesions are observed: marked hyperkeratosis, lichenoid aspect, and follicular pustulosis. Mucous membranes alterations, present for almost as long as 20 years, include stomatitis, chronic balanitis with ulcerative and keratotic lesions leading to synechiae; ocular abnormalities has had a follow up into lesions similar to those of cicatricial pemphigoid; direct immunofluorescence study in the vicinity of a buccal erosion showed a complement deposit on basement membrane; immunofluorescence studies on involved and uninvolved skin, and indirect immunofluorescence were negative. Several diagnosis were considered, in first place an atypical Reiter's syndrome. A part the possibility of a new entity, the most attractive hypothesis is this of a keratosis lichenoides chronica with severe mucous cicatrical lesions. A large number of treatment had been inefficacious but a clear improvement of keratotic lesions was noted with oral retinoid therapy.

[Normal proximal nail fold structure (author's transl)]. / Le repli sus-unguéal normal.

Normal structure of nail fold capillaries as observed by capillaroscopy and fluoroscopy is recalled. A procedure of proximal nail fold biopsy is described. The technique is simple without disadvantage for patients. Tissue from the proximal nail fold is studied in three different ways: light microscopy with histochemistry, electron microscopy and direct immunofluorescence. In the two normal cases studied, usual epidermal and dermal components are found. Some particular point may be emphasized: sweat's droplets draining of distal part of proximal nail fold, numerous and large nervous structures, capillaries basal lamina multiplication.

[Proximal nail fold biopsy in connective tissue diseases. 26 cases studied under light and electron microscopy and direct immunofluorescence (author's transl)]. / La biopsie du repli sus-unguéal dans les malsdies dites du collagéne. Etude histologique, ultrastructurale et en immunofluorescence de 26 cas.

30 specimens of nail fold biopsies have been studied through light and electron microscopy, and direct immunofluorescence, in 26 cases of connective tissue diseases: Raynaud's phenomenon and acrosclerosis (7 cases), systemic scleroderma (10 cases), chronic and acute lupus erythematosus (4 cases), dermatomyositis (5 cases). Numerous tissular changes have been observed by these three different ways: capillaries dilatations, dermal sclerosis, numerous, large, dermal and epidermal colloid bodies, basal lamina replications, collagen's modifications, tubuloreticular inclusions, crystalloid bodies, lysosomial inclusions, immunoglobulins deposits. Thus proximal nail fold appears to be an elective tissular area for collagen diseases study.

[Evaluation of oral retinoid preventive action on human cutaneous epitheliomas (author's transl)]. / Essai de prévention des épithéliomas cutanés par le rétinoïde aromatique.

Beneficial effects of oral retinoids in prophylaxis of epithelial neoplasias have been demonstrated by experimental works. In this study oral retinoid (RO 10-9359) was used in human dermatosis with high frequency of cutaneous malignancies: xeroderma pigmentosum with or without malignant neoplasias, Mibelli's porokeratosis with multifocal malignant degeneration, basal cell naevus syndrome with basal cell carcinomas, familial epithelioma of Ferguson-Smith and actinic keratosis. This work started in december 1977. Visible epitheliomas have been treated before trial. Initial dose of retinoid was 1 mg/kg daily, decreased depending on individual tolerance. Results were appreciated by comparising number of epitheliomas observed in years preceding retinoid therapy and number of them appearing during treatment; in two familial cases (basal cell naevus syndrom in twins and xeroderma pigmentosum in two brothers) comparison was made between treated and untreated patients. First results are very promising: an excellent response on solar keratosis is noted; epitheliomas occurrence seems actually to be prevented or delayed by oral retinoid therapy. Of course more numerous cases, a longer time, periods without treatment are necessary to confirm these interesting first results. On the other hand drug is not with this dose active on already constituted carcinomas.