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Background: Our objective was to describe the clinical, histological characteristics, and disease outcome of a cohort of mycosis fungoides (MF) diagnosed during childhood including disease status at adulthood. Methods: This is a retrospective multicentre survey of patients aged under 18 years at diagnosis with histologically confirmed MF. Patients’ clinical and histological characteristics, treatments, and disease outcome (for patients followed for more than 12 months) were analysed. Results: Forty-six patients were included (median age at diagnosis: 11 years; M:F sex ratio: 3:1) with 39 (85%) followed for at least 12 months. Thirty-nine patients (85%) had stage I MF. Hypopigmented patches were observed in 48% and folliculotropism in 43% patients. Immunophenotype of the skin infiltrate was predominantly CD8+ in 17% of patients. Initial management included a wait-and-see strategy in 6/39 (15%), skin-directed treatment in 27 (69%), and systemic treatment in 6 (15%) patients, respectively, with partial or complete clinical response (PR or CR) observed in 28 patients (72%). 14/39 patients (36%) relapsed after initial response. After a median follow-up period of 54 months, disease status at last news was PR or CR in 31/39 (79%), stable disease in 6 (15%), and progression in 2 (5%) patients. Histological transformation was observed in 3/39 (8%). Of the 15 patients followed until adulthood, 13 (87%) had persistent MF. Discussion: This survey confirms the high frequency of hypopigmented and folliculotropic lesions and of CD8+ immunophenotype compared to adult MF patients. The long-term course is usually indolent but transformation may occur sometimes long after disease onset and the disease may persist during adulthood.

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Applying next-generation sequencing to paired skin and marrow biopsies, Delaleu et al describe an entity they term “myelodysplasia cutis,” comprising histologic features of histiocytoid Sweet syndrome in the skin and a clonally related myelodysplasia in the bone marrow. This can be distinguished from forms of histiocytoid Sweet syndrome not associated with myelodysplastic syndromes, as well as classical neutrophilic Sweet syndrome associated with various malignant and nonmalignant diseases and leukemia cutis where the infiltrating cells are myeloblasts.

We describe a unique case of human T‐lymphotropic virus 1 (HTLV‐1)‐associated infective dermatitis‐like lesions in systemic lupus erythematosus. This suggests that some lupus patients may have immunological abnormalities resembling to those described in chronic HTLV‐1 infection.

Neutrophilic dermatoses (ND) are a group of conditions characterized by an aseptic accumulation of polymorphonuclear leukocytes in the skin. Occurrence of ND in association with myeloid malignancies, mainly myelodysplastic syndrome and myelogenous acute leukemia, is not rare and is often associated with a poor prognosis. Recent findings have improved understanding of the pathophysiology of myeloid malignancy-associated ND. We review the clinical spectrum of myeloid malignancy-associated ND with an emphasis on recently identified mechanisms. Myeloid leukemia cells retain the potential for terminal differentiation into polymorphonuclear leukocytes in the skin. Many studies suggest a clonal link between myeloid malignancies and ND. Activation of autoinflammatory pathways (NOD-like receptor family pyrin domain-containing-3, Familial Mediterranean Fever Gene) in the clonal cells of myeloid disorders may also be involved in this setting.

BACKGROUND Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) is a rare subtype of hereditary epidermolysis bullosa, with a poorly understood pathogenesis and no satisfactory treatment. OBJECTIVES To assess the clinical and biological features, genetic basis and therapeutic management, to better characterize this rare genodermatosis. METHODS We have conducted a retrospective study, reviewing the clinical presentation, genetic diagnosis, immunohistopathological findings and biological characteristics and management of patients with dystrophic epidermolysis bullosa pruriginosa. This study was conducted in the Department of Dermatology at Saint-Louis Hospital and the Department of Genetics at Necker Hospital (Paris, France). All patients with a diagnosis of DEB-Pr seen between 2010 and 2020 were included. RESULTS Seven patients were included, the average age of 50.1 years [range 36-76]. Pruriginous-lichenified papules, plaques or nodules appeared at 27.6 years on average [range 7-66] on pretibial areas and forearms, associated with milia and toenails dystrophy. All patients received multiple treatments, but none could sustainably reduce pruritus. Immunohistopathological analysis of lesion skin revealed subepidermal blister with fibrosis, milia and mast cell infiltration. Serum TNFα, IL1β and IL6 levels were elevated in 2/6 patients. Total serum IgE levels were increased in 7/7 patients, with no history of atopy. Immunophenotyping of circulating T-cells revealed an increased Th2 subset in 4/4 patients, with reduced Th1 and Th17 subpopulations. Genetic analysis of COL7A1 identified 7 distinct causative mutations, six of which were new. Intra-familial clinical variability was documented in 5/7 patients and was associated with the co-inheritance of a recessive COL7A1 mutation or an FLG2 mutation in 2 families. CONCLUSION Our study confirms the stereotyped presentation of DEB-Pr with large intra-familial variability in disease expression. Mast cell infiltration, elevated IgE and increased Th2 subset without atopy strongly support a role of Th2-mediated immunity in DEB-Pr, and further argue for new targeted therapeutic options such as dupilumab.

Introduction Les pemphigus (P) sont caracterises par des IgG diriges contre les desmogleines (Dsg), Dsg 1 (P. superficiel), ou Dsg 3 (P. profond). Des depots d’IgA peuvent etre observes, seuls (IgAs), ou associes a des IgG (IgA/G). Cette forme de P est rare et peu decrite. Son pronostic est mal connu. Nous rapportons des resultats cliniques d’une serie de 14 cas. Materiel et methodes Un appel a cas a ete lance au groupe Bulles. Les criteres d’inclusion etaient les P avec presence d’IgA en IFD, seuls ou avec IgG, entre le 01/01/2001 et le 31/01/2021. Les donnees cliniques, therapeutiques et evolutives ont ete recueillies retrospectivement. Une analyse histologique standardisee est en cours. Resultats Quatorze patients (10 centres) ont ete inclus : 9 F, 5 H, d’âge median 65 ans (18–85). Huit avaient un P IgAs et 6 IgA/G. Le delai diagnostique median etait de 7 mois (1–48). L’atteinte etait etendue (> 10 % de la surface corporelle) dans 11 cas. Dix patients avaient une atteinte cephalique, 4 une atteinte muqueuse. Les differences entre P IgAs et P IgA/G portaient sur l’âge (P IgAs plus âges), les pustules ou bulles a hypopion (6/8 IgAs, 1/6 IgA/G) et l’atteinte des plis (n = 5, tous IgAs). Deux patients avaient une polynucleose neutrophile ou eosinophile au diagnostic, 4 une gammapathie monoclonale (3 P IgAs : 2 pics IgG + IgM, 1 pic IgA et un P IgA/G : pic IgG). L’IFI standard et les ELISA anti-Dsg1 et 3 etaient negatifs chez tous les P IgAs (mais IFI IgA + chez un patient). Dans les P IgA/G, l’IFI etait + dans les 6 cas, avec ELISA Dsg1 + (n = 6) et Dsg3 + (n = 1). Parmi les 7 blots realises, un seul (IgAs) trouvait des anticorps anti-desmocollines. Dix patients ont recu une corticotherapie (CT) locale, 7 une CT generale, 11 de la dapsone et 5 du rituximab, avec des differences notables de prise en charge entre les deux groupes. Cinq P IgAs ont rechute, vs 1 P IgA/G. Un patient IgA/G a eu un thymome avec myasthenie (blot negatif) et un P IgAs a eu un carcinome bronchique (blot + BP230). Un patient IgAs a rechute avec des depots d’IgG seuls en IFD. Discussion Les P avec depots d’IgA forment un spectre allant du P a IgAs, dit « P a IgA » dans la litterature, au P a IgA/G, tres proche du P IgG, notamment du pemphigus superficiel. Les pustules ou bulles a hypopion concernent surtout les P IgAs. Tout comme dans les autres maladies bulleuses a IgA, l’IFI standard est peu sensible dans les P IgAs et les ELISA Dsg du commerce sont negatifs car ne detectent que les IgG. Des anticorps anti-descollines, decrits dans la litterature, sont presents chez un seul patient ici (IgAs). Dans notre etude, les P IgAs, majoritairement traites par dapsone et CT locale, ont plus souvent rechute que les P IgA/G, traites par CT generale et rituximab. Ainsi, la place du rituximab dans les P avec depots d’IgA (notamment IgAs) reste a preciser.

is missing (Short communication)

Introduction La maladie de Kimura (MK) est une affection rare, de cause inconnue impliquant probablement la voie de l’immunite de type 2 (Th2), associant des atteintes cutanees, ganglionnaires, glandulaires et renales. L’efficacite de la chirurgie et de traitements (ttt) immunosuppresseurs/modulateurs (ISM, principalement les corticoides, la ciclosporine, l’interferon α) a ete ponctuellement rapportee. Nous rapportons pour la 1e fois l’efficacite du dupilumab dans la MK. Materiel et methodes Deux patientes (cas 1 : 41, cas 2 : 72 ans) rapportaient une dermatose prurigineuse chronique faite de nodules (cas 1) et plaques (cas 2) indures du visage et de papulonodules excories du corps. Une hyper-IgE (cas 1) et une hypereosinophilie (HE, cas 2) etaient notees. L’examen histologique (lesions du visage) montrait un infiltrat dermique dense lymphocytaire diffus et nodulaire avec presence de follicules reactionnels, des polynucleaires eosinophiles, associes a des neutrophiles (cas 2), a des plasmocytes et avec une hyperplasie vasculaire (cas 1). Le diagnostic de MK de forme cutanee pure etait porte. Un ttt par dupilumab etait debute. Apres 4 mois, le prurit etait ameliore de 40 % (cas 1, EVA passant de 8 a 5/10) et 90 % (cas 2, EVA passant de 9 a 1/10), les lesions du visage s’etaient nettement desinfiltrees, l’atteinte du corps avait disparu (cas 2) ou s’etait stabilisee (cas 1). La tolerance du ttt etait excellente. Discussion Le dupilumab est un anticorps monoclonal ciblant la sous-unite a du recepteur a l’interleukine (IL)-4, commune a l’IL-4 et IL-13 valide dans le ttt de la dermatite atopique moderee a severe, avec un bon profil de tolerance. Plusieurs arguments plaident pour l’implication de l’immunite Th2 dans la pathogenie de la MK : – la frequence d’un terrain atopique et d’atteintes eczematiformes ou a type de prurigo (56 % des cas), mimant ainsi des pathologies Th2-mediees ; – l’existence d’une fibrose histologique (86 % des cas), pouvant etre le fait d’une reponse immunitaire Th2 (effet pro-fibrosant via l’activation du fibroblaste par l’IL-4/13) ; – la frequence de l’HE et de l’hyper-IgE, potentiellement due a l’activation de la voie Th2 ; – la documentation dans le sang de patients, en comparaison a des temoins sains, d’une surexpression de cytokines Th2 (IL-4/5/9/10/13) et d’une surrepresentation d’un contingent de lymphocytes T Th2 (CD4+ CD45RO+ C62L+) capables apres stimulation in vitro d’une secretion d’IL-4 et dans les ganglions atteints d’une expression d’IL-5. Ainsi : – les donnees arguant du role de l’immunite Th2 dans sa pathogenie ; – l’experience positive ici rapportee ; – le faible niveau de preuve d’efficacite des ISM usuels rendent envisageable le dupilumab comme ttt de la MK avec un bon profil de tolerance. Nos 2 cas presentant des MK cutanees pures, les effets du dupilumab sur les atteintes extra-cutanees de la MK restent a decrire.

Introduction Le diagnostic precoce de lymphome T cutane n’est pas toujours aise et repose sur un faisceau d’arguments cliniques, biologiques, histologiques et moleculaires. Le sequencage haut debit du TCR-beta permet par la reconnaissance de sequences CDR3 specifiques l’identification et la quantification de chaque clone T present dans un echantillon donne. Il existe encore peu d’etudes a ce sujet avec des resultats discordants et aucun critere diagnostic valide. Notre etude avait comme but de determiner pour cette technique des seuils optimaux pour les valeurs suivantes : frequence du clone T majoritaire dans la peau rapportee a l’echantillon total (TCF) et ratio entre la frequence du premier et du deuxieme clone T (RPF), avec comme objectif de developper de nouveaux algorithmes pour le diagnostic de lymphome T cutane. Materiel et methodes Nous avons analyse retrospectivement les donnees obtenues par le sequencage haut debit du TCR-beta dans des echantillons de biopsies cutanees realisees chez 144 patients entre 2013 et 2020. Le diagnostic de lymphome T cutane etait base sur des criteres internationaux valides. Nous avons inclus 101 echantillons de patients ayant un diagnostic de lymphome T confirme dont 47 MF stade I-IIA, 1 stade IIB, 4 stade III, 35 syndromes de Sezary, 8 lymphomes T agressifs (PTCL NOS ou CD8+) et 6 lymphoproliferations CD30+ (3 papuloses lymphomatoides et 3 lymphomes anaplasiques a grandes cellules). En complement 43 echantillons provenant de patients avec des pathologies inflammatoires etaient inclus. Les performances de la technique ont ete etudiees a l’aide de courbes ROC. Resultats Les meilleures performances diagnostiques etaient obtenues pour le TCF avec une AUC de 0,957 versus 0,929 pour le RPF. Les valeurs de TCF et RPF pour chaque categorie ont ete modelisees. Avec des seuils de TCF de 5 % et 25 %,la specificite pour le diagnostic etait de 95 % et 100 %, et la sensibilite de 89 % et 50 %. Il existait une correlation significative entre le TCF et l’importance de l’atteinte sanguine chez les patients SS (cellules TCD4 + CD26−, r = 0,59, p = 0,0008 ; T CD4 + CD7−, r = 0,45, p = 0,01 ; T CD4 + CD158k+, r = 0,4, p = 0,03) Discussion Le TCF obtenu par HTS-TRB est un critere robuste pour le diagnostic de lymphome T cutane et particulierement pour celui de MF, avec une sp de 95 % et une se de 89 % pour un seuil de 5 %. Une telle specificite permettrait un diagnostic precoce de lymphome T cutane dans des cas difficiles. Ces resultats sont meilleurs que ceux obtenus a l’aide de la PCR classique sur gel du TCR gamma qui sont entaches de nombreux faux negatifs et faux positifs. Des etudes multicentriques prospectives seraient necessaires pour la definition de criteres valides internationaux pour l’usage de cette technique dans le diagnostic de lymphome T cutane.

Introduction Dans les hemopathies myeloides, les polynucleaires neutrophiles (PNN) des syndromes de Sweet (SS) et les cellules malignes myeloides partagent un precurseur commun. Le concept de myelodysplasia cutis (MC) a ete introduit dans la litterature pour designer un infiltrat tumoral non blastique de la peau, chez des patients anterieurement diagnostiques comme ayant un SS histiocytoide dans le cadre d’un syndrome myelodysplasique (SMD). Le but de notre etude etait de caracteriser une cohorte de MC sur le plan clinique, pronostic, histologique, moleculaire et therapeutique. Materiel et methodes Il s’agit d’une etude retrospective, descriptive, monocentrique. Les patients inclus devaient avoir un SMD et une atteinte cutanee avec biopsie cutanee montrant des cellules myeloides immatures et la presence de mutation(s) associee(s) aux SMD identiques dans la moelle et dans la peau par sequencage haut debit. Resultats Sept patients etaient inclus (âge median de 68 ans au diagnostic de MC). La duree mediane entre le diagnostic de SMD et l’apparition de la MC etait de 11 mois. Quarante-trois pour cent des patients presentaient un tableau de papulonodules diffus et 57 % un tableau de plaques inflammatoires des membres ou du visage. Une corticodependance etait note dans 57 % des cas. L’azacytidine etait introduit chez 57 % des patients, avec une efficacite dans 100 % des cas sur le tableau de MC. En analyse univariee, les MC etaient significativement associees a des cytopenies plus profondes et des score IPSS de haut risque au diagnostic du SMD. Ces resultats n’etaient pas retrouves en analyse multivariee. L’ensemble des patients avaient un envahissement dermique perivasculaire de cellules myeloides immature avec anomalie de pseudo-Pelger-Huet, MPO+. Les analyses moleculaires trouvaient dans le tissu hematopoietique un total de 23 mutations dans 20 genes differents, 18 d’entre elles etaient trouvees dans la peau. Discussion Notre etude a permis une description detaillee clinique, pronostique, therapeutique, histologique et moleculaire des MC, qui sont caracterisees par un tableau clinique polymorphe et sensible aux agents hypomethylants.

IMPORTANCE: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently described severe adult-onset autoinflammatory disease that is associated with myeloid lineage-restricted ubiquitin-activating enzyme 1 (UBA1) somatic variations that primarily affect the skin (Sweet syndrome), cartilage, and bone marrow. Skin symptoms have been poorly described. OBJECTIVE: To better describe clinical and pathological skin manifestations and their pathophysiology in VEXAS syndrome. DESIGN, SETTING, AND PARTICIPANTS: This multicenter retrospective case series study of clinical and histological features of 8 patients with VEXAS syndrome and skin involvement was conducted in France from December 2007 to March 2021, with molecular data obtained from March to April 2022. Any UBA1 variations were detected by Sanger or next-generation sequencing that was performed on bone marrow and formalin-fixed paraffin-embedded tissue sections of skin lesion biopsies. RESULTS: All 8 patients were men, and the median age at symptom onset was 65.5 years (interquartile range, 54-76 years). All patients had neutrophilic dermatosis skin lesions, including tender red or violaceous papules, sometimes edematous, without fever, arthralgia, recurrence or pathergy, inflammatory edematous papules on the neck and trunk (sometimes umbilicated), and firm erythematous purpuric or pigmented infiltrated plaques and nodules. Three patients had livedo racemosa. The infiltrates were perivascular and consisted of mature neutrophils with leukocytoclasia, which were admixed with myeloperoxidase-positive CD163-positive myeloid cells with indented nuclei and lymphoid cells in all cases. A sequencing analysis of paired bone marrow samples and skin lesion biopsies identified the same loss-of-function UBA1 variation in both samples for all patients. CONCLUSIONS AND RELEVANCE: This case series study describes the different clinical presentations of skin lesions found in VEXAS syndrome, which is characterized histologically by neutrophilic dermatosis. The findings suggested that the dermal infiltrates seen in VEXAS skin lesions are derived from the pathological myeloid clone. This suggests that using therapies that target the pathological clone may be effective in the long-term management of the disease.

Folliculotropic mycosis fungoides (FMF) is a variant of mycosis fungoides (MF) characterized by the presence of atypical T cells in the hair follicles. FMF typically presents with hair loss, comedones, and cystic skin lesions. Syringotropic MF is defined by the eccrine gland infiltration by atypical T cells. Here we report a case of folliculotropic and syringotropic CD8 MF with exceptional diffuse mucosal involvement.

Chronic urticaria is a common skin disorder with heterogeneous causes. In the absence of physical triggers, chronic urticarial rash is called idiopathic or spontaneous. The objective of this study was to identify the molecular and cellular bases of a disease condition displayed by two unrelated patients aged over 60 years who presented for two decades with a chronic urticaria resistant to standard therapy that occurred in the context of systemic inflammation not triggered by cold. In both patients, a targeted sequencing approach using a next generation technology identified somatic mosaic mutations in NLRP3, a gene encoding a key inflammasome component. The study of several of both patients' cell types showed that, despite the late onset of the disease, NLRP3 mutations were not found to be restricted to myelomonocytic cells. Rather, the data obtained strongly suggested that the mutational event occurred very early, during embryonic development. As shown by functional studies, the identified mutations-an in-frame deletion and a recurrent NLRP3 missense mutation-have a gain-of-function effect on NLRP3-inflammasome activation. Consistently, a complete remission was obtained in both patients with anti-IL-1 receptor antagonists. This study unveils that in late-onset chronic urticaria, the search for autoinflammatory markers and somatic mosaic NLRP3 mutations may have important diagnostic and therapeutic consequences.

Introduction: Non–HIV-related visceral leishmaniasis (VL) is becoming increasingly prevalent in nontropical countries because of the increasing number of patients with chronic diseases and the development of immune-modulating drugs. Patient concerns: Case 1 is a 60-year-old male patient of Senegalese origin presented with weight loss, lymphadenopathy, anemia, and elevated lactate dehydrogenases. Case 2 is a 46-year-old male patient of Algerian origin, with a negative HIV serology presented with cutaneous lesions. Diagnosis: Patient 1: The diagnosis of stage IV lymphocytic lymphoma (LL) was confirmed by an inguinal nodal biopsy in 2013. Patient 2: The diagnosis of T-cell lymphoma was made in 2003. Interventions: Patient 1 received 5 cycles of bendamustine and rituximab followed by a complete remission. Patient 2 was initially treated with >10 different treatments followed by 8 different chemotherapy regimens due to the disease progression. Outcomes: Patient 1: In 2017, after a follow-up of 4 years, the patient presented with fever, lymphadenopathy, splenomegaly, and pancytopenia in the setting of hemophagocytic syndrome. The initial diagnosis was a relapse of lymphoma and the patient was treated with ibrutinib. His status worsened, and Leishmania DNA was detected by polymerase chain reaction (PCR) on the blood and bone marrow aspirates. Ibrutinib was stopped. Amphotericin B treatment induced a complete clinical remission and clearance of Leishmania DNA from the blood. Patient 2: In 2017, after a follow-up of 14 years, the patient presented with fever, lymphadenopathy, hepatosplenomegaly, pancytopenia with hemophagocytic syndrome, and an increase in the tumor skin lesions. A skin biopsy was taken from the face and the patient. A careful reexamination of the skin biopsy revealed the presence of Leishmania bodies. He was treated with 40 mg/kg liposomal amphotericin B leading to a regression of the clinical symptoms and negativation of the blood PCR. Conclusions: This case study shows that VL may be a diagnostic challenge in patients with lymphoma. Reactivation or primary infection should be considered in the differential diagnosis. The purpose of this study is to remind clinicians to think of VL in patients with systemic symptoms that could be misdiagnosed as a progression of the underlying lymphoma.

is missing (Short communication).

Mycosis Fungoides (MF) is a rare disease with a relatively good prognosis at early stage. However, skin lesions can impair quality of life due to extensive skin lesions. In some cases, skin lesions, and especially those of the face, become visible and change the physical appearance of the patients. This aspect can deeply affect patients psychologically and can impact their social life. Here, we report the case of a patient with multiple lesions including a disfiguring lesion arising from the nose. The extent of his skin lesions gave a palliative intent to his treatment project. The patient underwent several lines of chemotherapy and immunotherapy with poor results. He was then referred to our radiotherapy and received localized radiotherapy. Lesions disappeared completely within a few weeks. The patient reported a psychological relief. This case highlights the fact that radiotherapy can be done in a “palliative” intent in order to improve esthetic aspects of lesions that can dramatically impact the psychosocial side of patient’s life. Clinicians can consider radiotherapy as treatment of some MF lesions as far as they impair the patient’s comfort from a psychological and social point of view.