ABSTRACT
BACKGROUND: Scleromyxedema (SM) is a rare skin disorder related to monoclonal gammopathy. High dose intravenous immunoglobulins (HDIVIg) are usually used as a frontline therapy with initial efficacy. However, some patients evolve with relapse, refractory state or severe extra-cutaneous complications such as dermato-neuro syndrome (DNS) or cardiac involvement. The objective of the study is to evaluate the use of anti-plasma cell treatment in these patients in order to obtain a deep and durable dermatological and haematological response. METHODS: We report here eight patients treated with HDIVIg together with anti-plasma cell therapy including: lenalidomide and dexamethasone (n = 5); bortezomib, cyclophosphamide and dexamethasone (n = 1); daratumumab, lenalidomide and dexamethasone (n = 2). RESULTS: Combination of HDIVIg with a treatment targeting the monoclonal component led to a high level of haematological remission and drastically improved skin response with an acceptable safety profile in all patients. Moreover, HDIVIg was reduced and stopped in 4 of the 7 patients who achieved complete remission. CONCLUSIONS: The association of lenalidomide and dexamethasone with HDIVIg could improve the treatment of relapsed or severe SM.
Subject(s)
Dermatomyositis , Humans , Janus Kinase 1 , Dermatomyositis/drug therapy , Administration, Cutaneous , SkinABSTRACT
Neutrophilic dermatoses (ND) are a group of inflammatory skin conditions characterized by a neutrophilic infiltrate on histopathology with no evidence of infection. ND are classified based upon the localization of neutrophils within the skin and clinical features. Recent findings suggest that ND are due to two main mechanisms: i) a polyclonal hereditary activation of the innate immune system (polygenic or monogenic); or ii) a clonal somatic activation of myeloid cells such as encountered in myelodysplastic syndrome or VEXAS syndrome. ND belong to internal medicine as a great number of patients with ND suffer from an underlying condition (such as hematological malignancy, inflammatory bowel disease, auto-immune and auto-inflammatory diseases). ND are diagnoses of exclusion and physicians should always consider differential diagnoses, particularly skin infections. Here, we review the pathophysiology and classification of the main ND (i.e., subcorneal pustular dermatosis (Sneddon-Wilkinson Disease) and Intercellular IgA dermatoses, aseptic pustulosis of the folds, Sweet syndrome, neutrophilic eccrine hidradenitis, pyoderma gangrenosum, erythema elevatum diutinum, neutrophilic urticarial dermatosis and neutrophilic panniculitis), their clinical and histopathological features, and we highlight the investigations that are useful to identify ND-associated diseases and to exclude the differential diagnoses.
Subject(s)
Pyoderma Gangrenosum , Skin Diseases, Vesiculobullous , Sweet Syndrome , Vasculitis, Leukocytoclastic, Cutaneous , Humans , Sweet Syndrome/diagnosis , Sweet Syndrome/pathology , Pyoderma Gangrenosum/diagnosis , Skin Diseases, Vesiculobullous/diagnosis , Neutrophils/pathologyABSTRACT
BACKGROUND: Erythema multiforme (EM) is a muco-cutaneous inflammatory disease mainly triggered by herpes simplex virus (HSV) recurrences. Association of EM and circulating auto-antibodies against plakins (anti-PLK-Abs [EM-PLK+]) has been reported. However, little is known about this subset of EM. OBJECTIVES: We aimed to describe the clinical and immunological features and response to treatment of EM-PLK+. METHODS: We conducted a retrospective multicentric study of EM-PLK+ selected from the database of the immunological laboratory of Bichat hospital, Paris, France, from January 2009 to December 2020. Anti-PLK-Abs were detected in ≥1 immunological tests: immunofluorescence assay, immunoblotting and/or ELISA. Patients with alternative diagnoses were excluded. RESULTS: We included 29 patients (16 women, median age 25 [range 2-58] years). EM-PLK+ were mostly major (EM with ≥2 mucosal involvements; n = 24, 83%) and relapsing (≥2 flares; n = 23, 79%). Cutaneous lesions were target (n = 13, 54%) and target-like lesions (n = 9, 38%) with usual topography (acral, n = 19, 79%; limbs, n = 21, 88%). Mucosal lesions affected the mouth (n = 27, 96%) and genitalia (n = 19, 68%), with a median of 2 [range 0-5] mucous membranes. EM-PLK+ were suspected as certain or possible postherpetic (EM-HSV) in 19 cases (65.5%); no triggering factors were detected in 9 (31%) patients. Desmoplakin-I/II Abs were the most frequent anti-PLK-Abs (n = 20, 69%); envoplakin and periplakin Abs were detected in 11 and 9 cases. Relapsing EM-PLK+ (n = 23) were still active (≥1 flare within 6 months) in 13 (57%) patients despite immunosuppressive therapy (n = 8, 62%). Antiviral drugs were ineffective in preventing relapse in 15/16 (94%) EM-HSV. CONCLUSION: The rationale for anti-PLK-Ab detection in EM is not elucidated. More systematic research of anti-PLK-Abs is warranted to better understand whether this association reflects humoral immune activity in a subset of EM or is fortuitous, related to an epitope spreading process. However, EM-PLK+ seems to be associated with major and relapsing subtypes, and difficult-to-treat cases.
Subject(s)
Erythema Multiforme , Herpes Simplex , Humans , Female , Child, Preschool , Child , Adolescent , Young Adult , Adult , Middle Aged , Retrospective Studies , Erythema Multiforme/drug therapy , Simplexvirus , Herpes Simplex/drug therapy , Antiviral Agents/therapeutic use , RecurrenceSubject(s)
Embolization, Therapeutic , Pancreatitis , Abdominal Pain/diagnosis , Abdominal Pain/etiology , HumansSubject(s)
COVID-19 , Chilblains , Chilblains/epidemiology , Disease Outbreaks , Humans , Pandemics , SARS-CoV-2ABSTRACT
INTRODUCTION: Patients with systemic sclerosis (SSc) have an increased risk of malignancy. In this study, we aimed to analyze the prevalence of cancer, the risk factors and the impact on overall survival. PATIENTS AND METHODS: We analyzed clinical (history of cancer, toxic exposition, organ involvement), immunological and treatment data in a monocentric cohort of SSc patients followed between January 2004 and December 2017. RESULTS: Two hundred and ten patients with SSc were included. During the follow-up, twenty-one patients (10 %) were diagnosed with malignancies. The underlying malignancies were breast adenocarcinoma (n=6, 28%), lung cancer (n=6, 28%), colorectal (colic adenocarcinoma, carcinoid tumor of the appendix), ovarian and cervix uteri, melanoma, kidney and papillary thyroid carcinoma (one of each). The median time between the first visit and the diagnosis of cancer was 4 [2-10] years. The overall survival in SSc patients with cancer was not significantly different from patients without cancer, with median survival during the first quartile (75%) at 12 years for patients with cancer and 11.6 years for those without cancer (P=0.9). The history of renal scleroderma crisis (HR 10.99, IC95% [1.95-62.07]; P=0.006) and the presence of anti-topoisomerase I antibodies (HR 5.5, IC95% [1.40-21.67]; P=0.01) were associated with an increased risk of cancer, whereas the presence of gastroesophageal reflux was inversely associated with the cancer occurrence (HR 0.22, IC95% [0.056-0.867]; P=0.03). CONCLUSION: The history of renal scleroderma crisis and the positivity of anti-topoisomerase I antibodies were associated with an increased risk of cancer in SSc patients in this monocentric study.
Subject(s)
Neoplasms/etiology , Scleroderma, Systemic/complications , Adenocarcinoma/epidemiology , Adenocarcinoma/etiology , Adolescent , Adult , Aged , Analysis of Variance , Antibodies, Antinuclear/analysis , Breast Neoplasms/epidemiology , Breast Neoplasms/etiology , Child , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/etiology , DNA Topoisomerases, Type I/immunology , Female , Follow-Up Studies , Humans , Kidney Neoplasms/epidemiology , Kidney Neoplasms/etiology , Lung Neoplasms/epidemiology , Lung Neoplasms/etiology , Male , Melanoma/epidemiology , Melanoma/etiology , Middle Aged , Neoplasms/epidemiology , Ovarian Neoplasms/epidemiology , Ovarian Neoplasms/etiology , Prevalence , Prospective Studies , Retrospective Studies , Risk Factors , Scleroderma, Systemic/drug therapy , Scleroderma, Systemic/immunology , Scleroderma, Systemic/mortality , Smoking/adverse effects , Thyroid Cancer, Papillary/epidemiology , Thyroid Cancer, Papillary/etiology , Thyroid Neoplasms/epidemiology , Thyroid Neoplasms/etiology , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/etiology , Young AdultABSTRACT
The erythrodermic ulcerated form of mycosis fungoides (MF) is exceptional, and treatment of refractory cases is challenging. Brentuximab vedotin (BV) is a monoclonal antibody combined with monomethyl auristatin E, recently approved for the treatment of refractory CD30+ cutaneous T-cell lymphoma. We report a case of refractory MF in a 56-year-old man with a long history of large-plaque parapsoriasis, as revealed by psoriasiform erythroderma, treated initially with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) polychemotherapy, inducing a 2-year complete response. After relapse, interferon and gemcitabine were unsuccessful. Finally, treatment with BV was decided upon, despite the absence of CD30 expression. After three infusions of BV 1·8 mg kg-1 , we achieved a complete and stable response, allowing an allogeneic stem cell transplant. The patient is still in complete remission, 19 months after the graft. This case illustrates the possibility of using BV in refractory CD30- MF as a salvage therapy.
Subject(s)
Brentuximab Vedotin/therapeutic use , Hematopoietic Stem Cell Transplantation , Mycosis Fungoides/therapy , Remission Induction/methods , Skin Neoplasms/therapy , Biopsy , Chemotherapy, Adjuvant/methods , Drug Resistance, Neoplasm , Humans , Male , Middle Aged , Mycosis Fungoides/diagnosis , Mycosis Fungoides/pathology , Neoadjuvant Therapy/methods , Neoplasm Recurrence, Local , Skin/pathology , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Time Factors , Transplantation, Homologous , Treatment OutcomeSubject(s)
Immunologic Deficiency Syndromes/drug therapy , Lichen Planus/drug therapy , Salvage Therapy/methods , Sirolimus/therapeutic use , Administration, Oral , Adult , Betamethasone/therapeutic use , Biopsy , Drug Resistance , Drug Therapy, Combination/methods , Female , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunologic Deficiency Syndromes/immunology , Lichen Planus/immunology , Lichen Planus/pathology , Middle Aged , Photopheresis , Skin/pathology , Treatment OutcomeABSTRACT
Systemic sclerosis (SSc) is an autoimmune disease, characterized by fibrosis of the skin and other organs, vascular impairment and deficient immune responses. Mucosal-associated invariant T cells (MAIT) have been involved in various inflammatory and autoimmune diseases. The aims of this study were to determine the frequencies of MAIT cells in the blood of patients with systemic sclerosis (SSc) and to compare their distribution in different types of SSc. Blood samples from patients with SSc and healthy controls were examined by flow cytometer to analyse the frequencies of MAIT and γδ T cells. We demonstrate that in SSc the frequencies and absolute numbers of MAIT and γδ T cells are significantly reduced in comparison with healthy controls. MAIT and γδ T cells did not correlate with C-reactive protein, BNP, pulmonary involvement or median skin fibrosis scale, steroid amount or disease duration. In addition, MAIT and γδ T cells decrease did not stratify with gender, interstitial lung disease or active digital ulcers. Functional studies are necessary to determine the signification of MAIT cells decrease in systemic sclerosis.
Subject(s)
Blood Cells/immunology , Mucous Membrane/immunology , Natural Killer T-Cells/immunology , Scleroderma, Systemic/immunology , Skin/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Fibrosis , Humans , Immunity, Mucosal , Lymphocyte Count , Male , Middle Aged , Receptors, Antigen, T-Cell, gamma-delta/metabolism , Young AdultABSTRACT
INTRODUCTION: Hepatic glycogenosis is a rare syndrome, which includes poorly controlled diabetes mellitus, hepatomegaly, delayed puberty, and growth delay. Insulin edema is sometimes associated. CASE REPORT: An 18-year-old woman presented with diffuse edema, hepatomegaly, amenorrhea, uncontrolled diabetes, and elevated transaminases and cholestasis. Hepatic ultrasonography and abdominal computed tomographic scan confirmed the hepatomegaly. The liver biopsy showed a massive glycogenosis and the diagnosis of hepatic glycogenosis was confirmed. Too large doses of insulin were responsible of diffuse edema. Diabetes equilibration and diminution of insulin intakes allow correction of this disorder. CONCLUSION: Excess of insulin can lead to excessive hepatic glycogen storage by activation of glycogenosis enzymes. Biological manifestations consist on elevated liver enzymes and hyperlactatemia. There is a link between administration of high dose of insulin and edema. Hepatic glycogenosis should be suspected when diabetes is uncontrolled and be considered as a differential diagnosis of steatosis. It may be associated and revealed by insulin edema directly related to excessive insulin intakes.