F. Cordoliani

Pathogenesis and treatment of xanthomatosis associated with monoclonal gammopathy

Xanthomas are a common manifestation of lipid metabolism disorders. They include hyperlipemic xanthoma, normolipemic xanthoma, and a related condition, necrobiotic xanthogranuloma (NXG). All 3 forms can be associated with monoclonal immunoglobulin (MIg). In an attempt to improve diagnosis, understanding, and treatment of this association, we retrospectively analyzed a personal series of 24 patients (2 hyperlipemic xanthoma, 11 normolipemic xanthoma, and 11 NXG) and 230 well-documented reports from the literature. With the exception of the nodules and plaques featured in NXG, the clinical presentation of xanthomatous lesions usually resembled that seen in common hyperlipidemic forms and could not be used to suspect MIg-associated xanthomas. Extracutaneous sites were not rare. The MIg was an IgG in 80% of cases. Myeloma was diagnosed in 35%. Hypocomplementemia with low C4 fraction was present in 80% of studied patients. Low C1 inhibitor serum levels were found in 53%. Cryoglobulinemia was detected in 27%. These abnormalities suggest immune complex formation because of interactions between the MIg and lipoproteins and argue in favor of a causal link between MIg and xanthomas. Monoclonal gammopathy therapy could thus be an option. Indeed, among the patients who received chemotherapy, hematologic remission was accompanied by improvement in xanthoma lesions in several cases.

Successful Treatment in Two Cases of Steroid-Dependent Cutaneous Polyarteritis nodosa with Low-Dose Methotrexate

To the best of our knowledge, only 3 cases of cutaneous polyarteritis nodosa (PAN) treated successfully with methotrexate (MTX) have been reported in the medical literature. We report 2 further cases of steroid-dependent cutaneous PAN treated successfully with low-dose weekly MTX therapy. The clinical and biological tolerance of MTX was excellent. The cutaneous lesions started to regress within 3 weeks. One of the patients reported full recovery which lasted 2 years after stopping the therapy. So, MTX seems to be an interesting therapy in the treatment of PAN because of its relatively low toxicity, its simple use, its quick action and prolonged results after MTX has been stopped.

Relationship between cutaneous polyarteritis nodosa (cPAN) and macular lymphocytic arteritis (MLA): Blinded histologic assessment of 35 cPAN cases

BACKGROUNDnCutaneous polyarteritis nodosa (cPAN) is a skin medium vessel neutrophilic arteritis with livedo, nodules, and ulcerations. Macular lymphocytic arteritis (MLA) is a small arteritis with erythematous or pigmented macules and typical histologic features (a lymphocytic infiltrate, concentric fibrin ring, no disruption of the internal elastic lamina).nnnOBJECTIVEnWe sought to assess the frequency of clinical and histologic features of MLA in patients with cPAN.nnnMETHODSnThis was a monocentric retrospective analysis of patients given the diagnosis of cPAN with blinded assessment of skin biopsy specimens.nnnRESULTSnAll 35 patients included had an infiltrated livedo, nodules, or both. Ulceration was rare. Erythematous or pigmented lesions were present in 54% of patients. Predominantly lymphocytic arteritis, a paucity of neutrophils, concentric fibrin ring, and absence of internal lamina elastic disruption were present in 60%, 20%, 18%, and 23% of patients, respectively. Median follow-up was 11 years. None of the patients had systemic involvement, and 57% had a complete remission. The incidence of complete remission was not different between patients having a predominant lymphocyte infiltrate or few neutrophils.nnnLIMITATIONSnThis was a retrospective, monocentric study without a control group of patients with MLA.nnnCONCLUSIONSnOur data do not favor the classification of cPAN and MLA as distinct entities.

Blépharites du lupus érythémateux chronique: Quatre cas

Resume Introduction Le lupus erythemateux chronique atteint frequemment le visage, le cuir chevelu, les oreilles. L’atteinte des paupieres sous la forme d’une blepharite chronique est plus rarement decrite. Nous rapportons 4 observations de lupus erythemateux chronique avec atteinte palpebrale specifique. Dans un cas, il s’agissait de l’unique localisation de la maladie. Observations Quatre malades âges de 26 a 45 ans avaient une blepharite de la paupiere inferieure sous forme d’une plaque infiltree, erythemateuse et keratosique. Dans 2 cas l’atteinte palpebrale etait associee a d’autres lesions cutanees evocatrices de lupus erythemateux chronique. Dans un cas, cette blepharite existait depuis 2 ans, de facon isolee et avait ete biopsiee a 2 reprises sans qu’un diagnostic ne soit retenu. Dans un cas, la blepharite chronique constituait la seule lesion cutaneo-muqueuse depuis 4 ans, associee a des arthralgies de rythme inflammatoire, avant que des lesions alopeciques du cuir chevelu permettent le diagnostic de lupus. Le traitement par antipaludeens de synthese a permis une guerison des blepharites dans 3 cas. Un malade a ete traite par thalidomide avec succes apres l’echec des antipaludeens de synthese. Discussion L’atteinte palpebrale isolee est rare dans le lupus et peut entrainer un retard diagnostique considerable responsable de lesions cicatricielles definitives et de complications ophtalmiques. La plupart des auteurs signalent l’atteinte preferentielle de la paupiere inferieure, plus precisement son tiers externe. La semiologie est tres evocatrice puisqu’elle comporte generalement les 3 lesions elementaires du lupus erythemateux chronique : l’erytheme parfois telangiectasique, l’hyperkeratose ponctuee et plus tardivement l’atrophie. L’efficacite des antipaludeens de synthese est remarquable.BACKGROUNDnDiscoid lupus erythematosus is a chronic skin disease frequently involving the face, scalp and ears. Palpebral lesions are rare. We report 4 cases of this uncommon localization. In one case, palpebral lesions were the sole manifestation of the discoid lupus erythematosus.nnnCASE REPORTSnFour patients aged between 26 and 45 Years had lesions of the lower eyelid as erythematous, infiltrated and scaly plaques. One patient, without diagnosis despite 2 skin biopsies of lesion, presented with a 2-Year history of blepharitis in the absence of any other cutaneous abnormality. In one case, chronic blepharitis has been present for 4 Years and associated with inflammatory arthralgia. Alopecia occurred 4 Years after the onset of blepharitis and led to the diagnosis of discoid lupus erythematosus. In 2 cases, blepharitis was associated with typical cutaneous lesions of discoid lupus erythematosus. Antimalaria drugs were very effective in 3 cases. In one patient the antimalaria drug failed, but thalidomide was effective.nnnDISCUSSIONnThe location of lesions on the eyelids in the absence of any other cutaneous abnormality is rare and can easily lead to the misdiagnosis of discoid lupus erythematosus. Most Authors mention a predilection of the lesions to the inferior portion of the eyelid, more specifically to the external third. The involvement of the eyelids with permanent scarring and severe eye impairment is explained by the long duration of the disease without diagnostic and appropriate treatment. Clinical examination is highly consistent with discoid lupus erythematosus: the lesions typically present as well-circumscribed, erythematous plaques with telangiectasia and scales and atrophy in long-standing disease. Antimalaria drugs are remarkably effective.

Extensive human papillomavirus-related disease (bowenoid papulosis, Bowen's disease, and squamous cell carcinoma) in a patient with hairy cell leukemia: Clinical and immunologic evaluation after an interferon alfa trial

significance of mucin in sweat gland tumors. Br J Cancer 1952;6:363-8. 8. Kwittken J. Muciparous epidermal tumor. Arch Dermatol 1974;109:554-5. 9. Underwood JW, Adcock LL, Okagaki T. Adenosquamous carcinoma of skin appendages (adenoid squamous cell carcinoma, pseudoglandular squamous cell carcinoma, adenocanthoma of sweat gland of Lever) of the vulva: a clinical and ultrastructural study. Cancer 1978;42:1851-8. 10. Marsch WC, Rotter-Ross C. Cutaneous squamous cell carcinoma with unicellular mucoprotein accumulation. Dermatologica 1983; 166:294-300. II. Zak FG, Palladino YS. Muciparous metaplasia and primary mucoepidermoid skin tumors. Arch Dermatol 1969; 100:23-5. Journal of the American Academy of Dermatology October 1993

Maladie de Rosai-Dorfman à révélation cutanée : 7 observations

BACKGROUNDnRosai-Dorfman disease (RDD) is a benign form of non-Langerhans-cell histiocytosis. It is identified by a particular histological profile first observed in febrile lymph nodes. Extranodal sites are frequent. The most common site is the skin, which can reveal the disease despite a difficult and delayed diagnosis. Seven cases of cutaneous revelation of RDD were studied retrospectively in order to delineate the clinical characteristics and facilitate diagnosis and treatment of this extremely rare disease.nnnPATIENTS AND METHODSnSix cases of RDD from 1990 to 2011 were identified in the photographic and histopathological records of the Saint-Louis Hospital and one case came from a Bichat Hospital consultation. The diagnosis was based in all cases on histopathology results.nnnRESULTSnPatients consisted of four men and three women aged between 31 and 69 years. Cutaneous lesions (3 to 20) revealed the disease in all of them and the time from disease onset to diagnosis ranged from six months to five years. The clinical presentation was erythematous or orange popular nodules or plaques, usually on the face. Microscopically, a dense dermal infiltration was observed, in some cases extending into the subcutaneous tissue, with pale histiocytic cells characterised by emperipolesis, plasma cells, lymphocytes, some neutrophils and variable fibrosis. The diagnosis, initially erroneous in 4 cases, was rectified by a second reading of histopathology slides, and immunohistochemical studies showed expression of S-100 protein in histiocytes but not CD1a. Three patients had pure cutaneous RDD. Two neurological sites and one nasal site were also found, with one ENT site and sequelae of previous uveitis in one patient. All extra-cutaneous sites were identified by clinical examination. Different treatments were proposed according to the sites and impact of the disease. In one case, the lesions regressed spontaneously after 18 months.nnnCOMMENTSnFew RDD series have been published and they mainly concern Asian patients. The ethnic origin of our patients was varied. The main findings were: 1) common clinical findings (orange or erythematous papules or nodules, mostly on the upper body), which should alert the dermatologist and histopathologist to the possible diagnosis of RRD; 2) the possibility, already mentioned in the literature, of spontaneous regression and a good prognosis; 3) the need for thorough evaluation by thoracic, abdominal and cerebral CT (computed tomography) or more a PET (positron emission tomography) scan to screen for potentially dangerous visceral sites, and also clinical follow up.

Lésions sclérodermiformes dans la porphyrie cutanée tardive : six observations

BACKGROUNDnThe clinical features of porphyria cutanea tarda (PCT) are usually distinctive and include blistering on sun-exposed areas, fragile skin, hypertrichosis and hyperpigmentation. Sclerodermatous changes are much less common, and may either reveal PCT or else appear later. We carried out a retrospective study of the files of six female patients presenting such lesions.nnnPATIENTS AND METHODSnSix women (age: 45 to 72 years) were referred for sclerodermatous lesions on sun-exposed areas of the upper body. In four patients, these lesions revealed PCT and in the remaining two patients they were indicative of previously treated but relapsing PCT. Four had sclerodermatous skin changes mimicking morphea of the neck and neckline, the top of the back and the face, while one presented more diffuse facial and cervical sclerosis. Associated alopecia was seen in three patients. The last patient presented isolated sclerodermiform alopecia. Associated malar hypertrichosis was seen in five cases and facial hyperpigmentation was noted in three cases. Four exhibited no blisters, cutaneous fragility, milia or photosensitivity. Histological findings were consistent with morphea or scleroderma in all cases. All patients presented abnormal liver tests: cirrhosis was present in four cases (primitive biliary cirrhosis, alcoholic cirrhosis and hepatitis C) and fatty liver in two cases. In four cases, there was excessive alcohol intake. Uroporphyrin levels were above the normal range in all cases. Local corticosteroid therapy associated with phlebotomy and/or low-dose hydroxychloroquine resulted in complete normalisation of porphyrin levels in four patients, with complete resolution of the cutaneous lesions in two patients and partial improvement in the other two.nnnDISCUSSIONnSclerodermatous changes are uncommon in PCT. They are not always late and secondary to the process of healing of blisters but can in fact constitute the first cutaneous symptom of the disease while revealing the underlying liver disease. Even in the absence of blisters, photosensitivity or cutaneous fragility, a diagnosis of PCT must be suspected in a setting of sclerodermatous changes distributed on the neck and face, or the neckline, or scarring alopecia, if associated with abnormal liver tests. Skin biopsy to confirm the diagnosis of scleroderma may delay the diagnosis, which is in fact based on porphyrin level. Normalization of the latter parameter under treatment allows regression of lesions.

Melanoderma Revealing Primary Antiphospholipid Syndrome

Acute adrenal insufficiency is a rare complication of the primary antiphospholipid syndrome. We report a case of melanoderma of rapid onset revealing an addisonian crisis associated with primary antiphospholipid syndrome, which was associated with life-threatening hypercalcemia. Melanoderma does not belong to the clinical presentation of acute adrenal insufficiency. Its very rapid onset in our patient is probably due to her very high level of serum ACTH, in relation with her recent abortion.

Lichen plan linéaire de la face : six observations

Introduction Seules quelques observations isolees de lichen plan lineaire de la face sont decrites dans la litterature. L’eruption est hyperpigmentee et semble distribuee selon les lignes de Blaschko. Nous en rapportons six nouveaux cas. Materiel et methodes Il s’agit d’une etude retrospective monocentrique. Les dossiers de 6xa0patients consideres cliniquement comme atteints de lichen plan lineaire de la face ont ete etudies. Une recherche effectuee sur la base de donnees en ligne «xa0PubMedxa0» avec les mots clesxa0: «xa0linear AND lichen AND facexa0» a permis de colliger 14xa0observations de ce type mais une recherche plus approfondie trouve des cas similaires publies sous d’autres denominations. Resultats Les patients etaient 3xa0hommes et 3xa0femmes. L’âge moyen etait de 42xa0ans (29–63xa0ans). Le tableau clinique etait stereotype, avec un aspect de dermatose lineaire hyperpigmentee du visage. Il existait constamment un prurit initial modere. Les lesions siegeaient sur le menton dans 3xa0cas, la zone mandibulaire dans 1xa0cas et chez 2xa0patients du front au nez ou a la joue. La palpation ne trouvait aucune induration mais une evolution atrophique a caractere superficiellement deprime etait perceptible dans 5xa0cas. Un cas etait associe a un lichen plan pilaire du cuir chevelu dans une forme classique d’aspect pseudo-peladique. L’examen histologique cutane realise chez 4xa0patients montrait un tableau de lichen plan pilaire ( Fig. 1 ). Discussion Nous rapportons 6xa0nouvelles observations de lichen plan lineaire de la face, entite rare dont seuls 14xa0cas ont ete rapportes dans la litterature. Notre serie confirme le caractere pigmentogene et le tropisme folliculaire de cette variete de lichen, ainsi que l’evolution frequemment atrophique avec une legere depression des lesions. Un tel tableau stereotype a ete publie sous d’autres denominations ou fait discuter d’autres diagnostics (lichen plan lineaire pigmente, lichen striatus, voire atrophodermie de Moulin ou lupus cutane lineaire). Comme dans les cas de la litterature, l’eruption faciale est generalement isoleexa0; nous avons cependant note un cas d’atteinte du cuir chevelu dans une forme pseudo-peladique. En raison de la rarete de la maladie, il n’existe aucune strategie therapeutique consensuelle. Le pronostic est incertain et l’atrophie, quand elle existe, est permanente. Conclusion Notre etude confirme que le lichen plan lineaire de la face, entite tres rare, est generalement un lichen folliculaire et pigmentogene d’evolution atrophiante.

Facteurs de risque et caractéristiques cliniques et microbiologiques de la tuberculose cutanées : étude rétrospective de 29 cas confirmés en culture

Introduction Le diagnostic de tuberculose cutanee (TBC) peut etre difficile. La presentation clinique est variee, les criteres histologiques peu specifiques et la culture des mycobacteries parfois negative, ce qui represente un probleme compte tenu de la recrudescence des tuberculoses multiresistantes. Il nous a semble interessant d’etudier les aspects epidemiologiques, clinico-pathologiques et microbiologiques de laTBC en France metropolitaine. Materiel et methodes Etude retrospective monocentrique des TBC avec preuve bacteriologique dans un CHU entre1995 et 2012. Resultats Vingt-neuf patients ayant une TBC prouvee par culture de biopsie cutanee ont ete inclus. Ils etaient âges de 9 a 87xa0ans (moyenne 41xa0ans), avec un sex-ratio de 1,6. La duree d’evolution avant le diagnostic variait de 1xa0mois a 14xa0ans. Parmi les 25 patients d’origine geographique connue, 23 etaient des migrants venant de zones de prevalence elevee, notamment Afrique du nord,xa0Afrique sub-saharienne et Asie de l’estxa0; seuls 2 etaient originaires de France metropolitaine. Aucun patient n’etait seropositif pour le VIHxa0; 2 rapportaient un antecedent de tuberculose et seulement 17xa0% avaient d’autres facteurs d’immunodepression. L’aspect clinique le plus frequent etait l’abces tuberculeux ou gomme ( n xa0=xa013), suivi du scrofuloderme ( n xa0=xa08) et du lupus tuberculeux ( n xa0=xa05). Une atteinte extra-cutanee concomitante etait presente dans 73xa0% des cas. L’IDR a la tuberculine, pratiquee chez 21 patients, etait positive dans tous les cas, et phlyctenulaire dans 11. Le test Quantiferon ® etait negatif dans 2 des 4 cas ou il etait pratique, comprenant un patient a l’IDR phlyctenulaire. Les biopsies cutanees montraient des granulomes tuberculoides avec necrose caseeuse dans la majorite des lesions gommeuses, cette necrose etant inconstante dans les lesions de scrofuloderme et absente dans les lupus tuberculeux. La coloration de Ziehl-Neelsen n’etait positive que dans 3 cas (10xa0%), tous etant des gommes. L’antibiogramme, realise chez 27 patients, montrait une resistance a l’isoniazide (IZD) dans 4 cas mais aucune mycobacterie multiresistante. Discussion Malgre les limites liees a son caractere retrospectif monocentrique, cette etude met en evidence quelques points d’importance pratiquexa0: diversite des presentations cliniques, predominance de l’origine geographique parmi les facteurs de risque, rarete des facteurs classiques d’immunodepression, notamment le VIH, faible valeur negative du test Quantiferon ® , frequence des atteintes viscerales associees, absence de bacterie multiresistante mais possibilite de resistance a l’IZD. Conclusion La TBC bacteriologiquement prouvee presente en France des caracteristiques propres utiles a connaitre. Toutefois, il n’est pas certain que ces caracteristiques se retrouvent dans les formes avec culture negative ou les «xa0tuberculidesxa0», qui necessiteraient des etudes specifiques.