Epidemiological changes in cutaneous lymphomas: an analysis of 8593 patients from the French Cutaneous Lymphoma Registry.

BACKGROUND: Primary cutaneous lymphomas (PCLs) are a heterogeneous group of T-cell (CTCL) and B-cell (CBCL) malignancies. Little is known about their epidemiology at initial presentation in Europe and about potential changes over time. OBJECTIVES: The aim of this retrospective study was to analyse the frequency of PCLs in the French Cutaneous Lymphoma Registry (GFELC) and to describe the demography of patients. METHODS: Patients with a centrally validated diagnosis of primary PCL, diagnosed between 2005 and 2019, were included. RESULTS: The calculated incidence was unprecedently high at 1·06 per 100 000 person-years. The number of included patients increased yearly. Most PCL subtypes were more frequent in male patients, diagnosed at a median age of 60 years. The relative frequency of rare CTCL remained stable, the proportion of classical mycosis fungoides (MF) decreased, and the frequency of its variants (e.g. folliculotropic MF) increased. Similar patterns were observed for CBCL; for example, the proportion of marginal-zone CBCL increased over time. CONCLUSIONS: Changes in PCL frequencies may be explained by the emergence of new diagnostic criteria and better description of the entities in the most recent PCL classification. Moreover, we propose that an algorithm should be developed to confirm the diagnosis of PCL by central validation of the cases.

[Digital ischaemia with fingertip ulcers during ipilimumab therapy]. / Ischémie digitale avec ulcération pulpaire sous ipilimumab.

BACKGROUND: Anti-cancer drugs have many adverse effects including vascular side effects. Herein we present the case of a patient presenting digital ischaemia with high imputability of ipilimumab. OBSERVATION: A 47-year-old male patient was treated for popliteal melanoma, initially stage IIIA but which subsequently became metastatic (stage IV), and for which ipilimumab was given after the failure of two lines of chemotherapy. During the 4th course of ipilimumab, the patient developed autoimmune hepatitis. Ipilimumab was suspended. Three months later, he developed a drug-like neuropathy followed one month later by ulceration of the right index finger. Causes of embolic, autoimmune and occupational origin (thrombotic microangiopathy, thrombosed aneurysm) were rapidly ruled out. Although a paraneoplastic origin could not be formally excluded, drug-induced immune disorder remained the most plausible origin. DISCUSSION: This is the first reported case of digital ulceration under ipilimumab.

[Granulomatous periocular eruption]. / Dermatite périoculaire granulomateuse.

BACKGROUND: Herein, we report a case of atypical periorificial dermatitis in a patient that had been receiving treatment for some time for atopic dermatitis. The specific feature of this rash was its periocular predominance with no perioral involvement, its clinical aspect and its histological picture evocative of sarcoidosis. PATIENTS AND METHODS: A 33-year-old man was being treated for a atopic dermatitis limited to the face and poorly responsive to dermal corticosteroids. Treatment was initiated with topical tacrolimus 0.1%. After 4 years, dependence on this treatment was noted, with daily application being needed to control the lesions. One year later, symmetric lesions were seen on the eyelids and periorbital regions; these were erythematous, micropapular and poorly delineated in a setting of oedema. Biopsy revealed epithelioid granulomatous inflammation, and, to a lesser degree, sarcoidal giant-cell features without caseous necrosis. Staging tests to identify systemic sarcoidosis were negative. Treatment with hydroxychloroquine at 400mg per day and discontinuation of topical tacrolimus resulted in complete remission of the lesions within 2 months. Hydroxychloroquine was discontinued after 6 months, and no relapses had occurred after 2 years of follow-up. DISCUSSION: Three diagnostic hypotheses may be posited for these granulomatous facial lesions. We opted for a diagnosis of granulomatous periorificial dermatitis despite the fact that exclusively periorbital involvement is rare (this condition is generally associated with perioral dermatitis). The second was that of pure cutaneous sarcoidosis, but the topography and clinical appearance of the lesions did not correspond to any of the cutaneous forms classically described. The third was that of tacrolimus-induced granulomatous rosacea, but the histological picture is different. CONCLUSION: The present case underscores the fact that a histological appearance of sarcoidosis on skin biopsy may be associated with perioral dermatitis.

Blastic plasmacytoid dendritic cell neoplasm: clinical features in 90 patients.

BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease characterized by malignant proliferation of a contingent blastic plasmacytoid dendritic cell. This rare entity is recognized mostly by cutaneous spreading, or not having a leukaemic component. The prognosis is very poor. OBJECTIVES: To study a large cohort of 90 patients with BPDCN, to define additional symptoms to form a correct diagnosis earlier, and to manage such patients accordingly. METHODS: We retrospectively reviewed BPDCN cases registered in the French Study Group on Cutaneous Lymphoma database between November 1995 and January 2012. Ninety patients were studied. Demographic data, clinical presentation, initial staging and outcome were recorded. RESULTS: The group contained 62 male and 28 female patients (sex ratio 2·2). Their ages ranged from 8 to 103 years at the time of diagnosis (mean 67·2 years). Three major different clinical presentations were identified. Sixty-six patients (73%) presented with nodular lesions only, 11 patients (12%) with 'bruise-like' patches and 13 (14%) with disseminated lesions (patches and nodules). Mucosal lesions were seen in five patients (6%). The median survival in patients with BPDCN was 12 months. CONCLUSIONS: We here distinguish three different clinical presentations of BPDCN. A nodular pattern is a more common feature than the originally reported 'bruise-like' pattern. Despite the fact that BPDCN may initially appear as a localized skin tumour, aggressive management including allogeneic bone marrow transplantation should be considered immediately, as it is currently the only option associated with long-term survival.

[Febrile cellulitis surrounding a scar revealing a large immunoblastic B-cell lymphoma]. / Dermohypodermite fébrile péricicatricielle révélatrice d'un lymphome B immunoblastique à grandes cellules.

BACKGROUND: Secondary skin sites of lymphoma appear in the advanced stages of the disease. We report the first case of a pericicatricial skin infiltration, mimicking febrile dermohypodermitis, revealing diffuse immunoblastic large B-cell non-Hodgkin's lymphoma. PATIENTS AND METHODS: Four months after decompressive cervical laminectomy, a 56-year-old man presented an inflammatory pericicatricial patch evoking cellulitis in a setting of hyperthermia and lymphadenopathy. Blood cultures and bacteriological analysis of skin biopsy samples were negative. The images showed infiltration of the soft subcutaneous areas and polyadenopathy. Two weeks later, several subcutaneous nodules appeared on the trunk. Histological analysis and immunolabelling pointed to immunoblastic large B-cell non-Hodgkin's lymphoma. A clone of B lymphocytes CD45+, CD20+, CD79a+, Bcl2+, CD5+, MUM1+, CD3-, CD10-, CD23- and Bcl6- was seen. The remainder of the extension examination was negative. CHOP-rituximab polychemotherapy resulted in complete regression of all lesions, notably the inflammatory cervical plaque. DISCUSSION: Secondary skin manifestations of lymphoma are generally non-specific (pruritus, ichthyosis, purpura, etc.) rather than specific in terms of lymphoid infiltration. As in our patient, certain cutaneous sites of lymphoma may have a misleading clinical presentation, histological analysis alone was able to provide a conclusive diagnosis. In our patient, the highly specific infiltration seen around the entire scar could either suggest a Koebner phenomenon or point to a role of the cutaneous aggression within the development of an inflammatory process contributing to pericicatricial infiltration by lymphoid cells. Locoregional invasion from the osseous part of the cervical spine and not macroscopically diagnosed during neurosurgery could also be responsible.

[Dermatologic follow-up and evaluation of skin tumours in renal transplant patients]. / Evaluation du suivi dermatologique et des tumeurs cutanées chez les greffés rénaux.

BACKGROUND: Renal transplant patients are at increased risk for warts, actinic keratoses and carcinomas. A descriptive study was conducted to investigate the number and frequency of dermatologic examinations in renal transplant patients with a functional graft. The incidence and clinical factors for skin tumours were also assessed. PATIENTS AND METHODS: We sent an initial questionnaire to 686 renal transplant patients asking whether they had consulted a dermatologist since the time of transplantation. A second questionnaire was then sent to private dermatologists in order to evaluate dermatologic follow-up and the frequency and anatomic distribution of warts and cancerous skin lesions. At the same time, the patients' medical records at the hospital were studied. RESULTS: About two thirds of the 436 patients included in the study have seen a dermatologist at least once since the time of transplantation. Only 31.2% are being followed up regularly by a dermatologist. The incidence of warts and actinic keratoses is 48.8% and 20.6% respectively, and increases with the duration of immunosuppressive therapy. The incidence of carcinomas is 20.2%, with basal cell carcinomas being seen more frequently than other carcinomas. Risk factors identified for carcinomas are older age at transplantation, duration of immunosuppressive therapy, fair skin, presence of warts and actinic keratoses. All these skin lesions arise predominantly on highly sun-exposed surfaces. Nevertheless, squamous cell carcinomas are more often confined to sun-exposed skin than Bowen's diseases and basal cell carcinomas. DISCUSSION: Dermatologic follow-up of transplant recipients has rarely been investigated and our study shows that monitoring of skin cancer is probably inadequate. It also confirms the high incidence of carcinomas among renal-transplant recipients in a temperate climate, although basal cell carcinomas are more frequent than squamous cell carcinomas.

[CDKN2A gene mutation and loss of p16 protein activity in a patient on levodopa presenting sporadic multiple primary melanoma]. / Mutation du gène CDKN2A et perte d'activité de la protéine p16 chez un malade traité par L-Dopa et atteint de mélanomes sporadiques multiples.

BACKGROUND: Cutaneous melanoma is a complex disease involving genetic and environmental factors. Levodopa has been incriminated in the development and/or progression of melanoma. OBSERVATION: We report the case of a man treated with levodopa and a dopadecarboxylase inhibitor for Parkinson's disease and presenting 22 cutaneous melanomas over a 4-year period. The patient is of phototype II and presents multiple nevi. Genetic analysis of predisposing genes demonstrated a CDKN2A mutation with loss of p16 activity. DISCUSSION: Multiple melanomas may be associated with genetic predisposition, and screening for the latter should be performed. The exceptionally high number of melanomas developed by our patient raised suspicions about levodopa, a precursor in melanin synthesis, as a potential inducer. Increased dermatologic controls and screening for predisposing genetic factors appear to us to be warranted in the event of melanoma development in patients on levodopa.

[Acrodermatitis enteropathica-like syndrome secondary to branched-chain amino acid deficiency during treatment of maple syrup urine disease]. / Pseudo-acrodermatite entéropathique secondaire à un déficit en acides aminés ramifiés au cours du traitement d'une leucinose.

INTRODUCTION: Clinical pictures resembling acrodermatitis enteropathica have been described in acquired zinc deficiency and deficiencies of other nutrients such as biotin, essential fatty acids and amino acids as well as biotin metabolism disorders. We describe the case of an infant with maple syrup urine disease who developed an acrodermatitis-like syndrome due to iatrogenic valine and isoleucine deficiency. CASE-REPORT: A diagnosis of maple syrup urine disease was made in a 5-month-old infant girl with severe neurologic disorders with extremely high levels of the three branched-chain amino acids (leucine, valine and isoleucine) in plasma and urine. Seven days after the start of therapy with a diet excluding these branched-chain amino acids, plasma isoleucine and valine concentrations were low while plasma leucine remained elevated. At the same time, a periorificial and acral dermatitis appeared together with diarrhea. Serum zinc concentrations were normal. A diagnosis of acrodermatitis enteropathica-like syndrome secondary to isoleucine and valine deficiency was suspected. Valine and isoleucine supplementation resulted in rapid resolution of the eruption. DISCUSSION: Several cases of acrodermatitis enteropathica-like eruptions resulting from therapeutic protein restriction diets have been described in infants with different aminoacidopathies. The accompanying dermatosis was associated with a raised plasma leucine/isoleucine ratio and/or isoleucine deficiency, or valine deficiency. While the exact pathogenesis of the skin lesions has not been established, these observations show that branched-chain amino acids are essential for normal growth and differentiation of keratinocytes. The essential role of isoleucine is further substantiated by the fact that its presence is critical in keratinocyte culture media, with growth arrest occurring upon its depletion.

[Skin cancer and psoralen plus UVA: a retrospective study of 106 patients exposed to a great number of PUVA treatments]. / PUVAthérapie et cancers cutanés: etude rétrospective chez 106 malades ayant reçu des doses élevées de PUVA.

INTRODUCTION: The benefits of PUVAtherapy in many dermatological affections are well known. Its carcinogenic role in the long term has been assessed varyingly in American and European series. OBJECTIVE: The aim of this study was to assess the role of PUVA in the onset of cancers of the skin. METHODS: Retrospective study of patients presenting with psoriasis and followed-up in the phototherapy unit of the Michallon Hospital in Grenoble since 1976 and having received more than 150 sessions of PUVA. The parameters studied were: age, gender, phototype, age at the time of the first irradiation, type of phototherapy administered, total number of sessions, concomitant treatments, administration of retinoids and the appearance of skin cancers with the interval before their onset after the first session, their localization and their histological type. RESULTS: One hundred six patients were retained among the 152 who replied to the inclusion criteria. Having died or been lost to follow-up, forty-six patients were excluded. Fourteen patients had presented at least one cutaneous tumor with a total number of 35. Excluding the keratoacanthomas, 13 patients had a non-melanic cutaneous cancer with a total number of 32 tumors. Ten out of the 14 were phototype III, 3 were phototype II and one was phototype IV. Nine out of 14 had received PUVAtherapy alone and 5 PUVAtherapy and broad spectrum UVB. The number of sessions of PUVA received in all the cases was more than 200 (220 to 780), corresponding to a total dose of UVA comprised between 1460 and 3882 Joules. The delay before onset of the tumors varied from 6 to 27 years after the first PUVAtherapy. The mean age at the time of the first irradiation was of 50.2 years (14-75 years). The mean duration of phototherapy was of 10 years (2.23 years).

[A persistent ulceration after a fortuitous BCG revaccination]. / BCGite après une revaccination accidentelle par le BCG.

INTRODUCTION: We report a cutaneous ulceration which occurred following a BCG revaccination. OBSERVATION: A 17 year old man, without previous history, presented a large and slow progressive ulceration of the left deltoid area following a fortuitous BCG revaccination. He did not complain of any other symptom. The swab culture from the exudate isolated Mycobacterium bovis whereas the direct analysis by Ziehl staining was negative. The ulceration healed in four months with local and systemic treatment with isoniazid. DISCUSSION: BCG vaccination side effects are largely described and can be either nonspecific, like with all vaccinations, or specific and due to the infection with Mycobacterium bovis. It can behave like an infectious agent or an immunogenic agent. The BCG revaccination complications are much less known because there are only few publications in the literature. In our case, the mechanism may have been infectious or imply immune reaction with Arthus'type-phenomenon and/or a type IV hypersensitivity. CONCLUSION: Adverse reactions due to revaccination are rarely described should became less frequent when the BCG revaccination is abandoned following the decision of French regulatory authorities. Nevertheless, such complications can occur by accident, as the case in our patient.

[Vogt-Koyanagi-Harada syndrome: a serious and rare emergency in children]. / Le syndrome de Vogt-Koyanagi-Harada: une urgence ophtalmologique grave et rare chez l'enfant.

Uveitis in children is a rare disease, often going undiagnosed. Vogt-Koyanagi-Harada syndrome, a uveomeningeal disease from an autoimmune process, rarely affects children, but an early diagnosis is essential in order to begin systemic corticosteroid therapy within the shortest delay possible for a better visual prognosis. We report a case of a 10-year-old boy, already treated with corticosteroids for the last 3 years for a nephrotic syndrome, referred for a sudden decrease in visual acuity affecting both eyes, associated with typical cutaneous manifestations of the disease.

[Two cases of iatrogenic cutis and subcutis calcinosis after calcium-containing heparin injection]. / Calcinose cutanée et sous-cutanée après injection d'héparine calcique : à propos de deux cas.

BACKGROUND: Subcutis calcinosis, characterized by abnormal calcium deposition in the skin, is a rare side effect of calcium containing heparins. PATIENTS AND METHODS: Two patients with renal failure presented skin lesions after receiving a calcium-containing heparin treatment. The first patient exhibited erythematous nodules on the abdomen and the second a large erythematous induration of the abdomen and nodules on the thighs. Both had normal blood analysis. The diagnosis of subcutis calcinosis was confirmed by the histological exam showing calcium deposit in the dermis and hypodermis. Outcome was unfavourable in one of the patients who developed a superinfection and skin necrosis lesion requiring surgery at 2 months. DISCUSSION: Subcutis calcinosis is a rare and probably underdiagnosed disease. To our knowledge, only 10 cases have been reported. The pathogenesis is not well-known, tissue damage and calcium disorders are considered as risk factors. The differential diagnoses that can be suspected include calciphylaxis, such as calcifying panniculitis and other local side effects of heparins. Outcome is usually favourable without treatment. CONCLUSION: We describe two cases of iatrogenic subcutis calcinosis after injections of calcium-containing heparins, including the second case of poor outcome. Clinicians should be aware of this adverse effect since other heparins such as fondaparinux or low-weight molecular heparins are contraindicated in patients with renal failure, leading to a large prescription of calcium-containing heparins in this population.