Clinical features and survival of patients with indolent systemic mastocytosis defined by the updated WHO classification.

BACKGROUND: In indolent systemic mastocytosis (ISM), several risk factors of disease progression have been identified. Previous studies, performed with limited patient numbers, have also shown that the clinical course in ISM is stable and comparable to that of cutaneous mastocytosis (CM). The aim of this project was to compare the prognosis of patients with ISM with that of patients with CM. METHODS: We employed a dataset of 1993 patients from the registry of the European Competence Network on Mastocytosis (ECNM) to compare outcomes of ISM and CM. RESULTS: We found that overall survival (OS) is worse in ISM compared to CM. Moreover, in patients with typical ISM, bone marrow mastocytosis (BMM), and smoldering SM (SSM), 4.1% of disease progressions have been observed (4.9% of progressions in typical ISM group, 1.7% in BMM, and 9.4% in SSM). Progressions to advanced SM were observed in 2.9% of these patients. In contrast, six patients with CM (1.7%) converted to ISM and no definitive progression to advanced SM was found. No significant differences in OS and event-free survival (EFS) were found when comparing ISM, BMM, and SSM. Higher risk of both progression and death was significantly associated with male gender, worse performance status, and organomegaly. CONCLUSION: Our data confirm the clinical impact of the WHO classification that separates ISM from CM and from other SM variants.

Disease spectrum in patients with elevated serum tryptase levels.

BACKGROUND: Elevated serum tryptase levels can be a sign of mastocytosis, which is a rare disease associated with systemic and/or skin manifestations. OBJECTIVE: To investigate patients with elevated tryptase levels in regard to their underlying diseases, and to determine whether increased tryptase can be used as a diagnostic marker for underlying mastocytosis. METHODS: In a retrospective study the data of 96 patients with serum tryptase levels higher than 15 µg/L were systematically analysed. In 48 patients control investigations for baseline tryptase were performed. RESULTS: Fifty-three of the 96 patients had tryptase levels ≥20 µg/L. A mere 16% of the 96 patients suffered from mastocytosis and had the highest tryptase levels (P < 0.001). The remaining patients had anaphylaxis (36%), urticaria and angioedema (26%), local reactions to insect bites (4%), drug reactions (3%), or miscellaneous diagnoses (15%). Only 16 of these had acute symptoms at tryptase investigation. In all, 48 patients had a follow up; in 7/48 patients with acute symptoms normal tryptase levels were seen at control investigations, but 41/48 (85%) patients showed continuously elevated tryptase levels >15 µg/L and in 30 patients (62%) even values >20 µg/L; 11 of these patients had anaphylaxis, five urticaria, five other diagnoses and nine patients mastocytosis. CONCLUSION: More than 50% of patients with non-mastocytosis such as urticaria and angioedema, drug or anaphylactic reactions repeatedly had tryptase levels higher than 20 µg/L. Since baseline tryptase >20 µg/L is a minor criterion for mastocytosis, these patients should be inspected for skin lesions of mastocytosis and receive a diagnostic body work-up for systemic mastocytosis including a bone marrow biopsy.

Retrospective long-term follow-up in patients with chronic palmoplantar dermatoses after good response to bath PUVA therapy.

BACKGROUND: Numerous studies have confirmed the short-term effectiveness of 8-methoxypsoralen bath PUVA therapy in patients with chronic palmoplantar dermatoses; however, little is known about long-term results. PATIENTS AND METHODS: In this retrospective study we examined the long-term results in 79 patients (mean age: 48 years) with chronic palmoplantar dermatoses who were treated with bath PUVA three times a week over an 8-year period. A good clinical response (a reduction of more than 50% of the skin lesions) occurred after a mean of 23 treatments and a mean cumulative UVA dose of 39 J/cm(2) in 51 patients (65%). In 2007 a questionnaire was sent to these 51 patients to assess the long-term outcome. RESULTS: With bath PUVA treatment, the best results were found in patients with hyperkeratotic eczema (17/22; 77% good clinical response) followed by patients with palmoplantar psoriasis (26/41; 63%) and patients with dyshidrotic eczema (8/16; 50%). Thirty-four patients (67%) answered the questionnaire after a mean follow-up interval of 4.3 years (10-87 months). Among these patients, 36% reported an improved course of disease after PUVA therapy with reduced frequency and/or intensity of the skin rash, and 29% of patients reported continued complete clearance. 79% of our patients reported a long-term reduction in the use of topical corticosteroids during the follow-up period (mean: 4.3 years). In addition, 67% of patients reported a lasting improvement in quality of life. CONCLUSIONS: These data show that bath PUVA may have a long-term, beneficial influence on the course of disease in a majority of patients with recalcitrant chronic palmoplantar dermatoses.

Clinical Impact of Skin Lesions in Mastocytosis: A Multicenter Study of the European Competence Network on Mastocytosis.

Mastocytosis is a rare neoplasm characterized by the expansion and accumulation of mast cells in various organ systems. Systemic mastocytosis (SM) may or may not present with cutaneous lesions. To examine the frequency and clinical impact of cutaneous involvement, data on 1,510 patients with mastocytosis collected in the registry of the European Competence Network on Mastocytosis were analyzed. Cutaneous involvement was found in 1,195 of 1,510 patients (79.1%). Of these, 286 had cutaneous mastocytosis, and 721 had SM with skin involvement. Adult patients with skin involvement who did not have a bone marrow examination (n = 188) were defined as having mastocytosis in the skin. In 315 patients, SM without skin involvement was found. The percentage of cases with cutaneous involvement was higher in indolent SM (100%) and smoldering SM (87.9%) compared to aggressive SM (46.8%) or mast cell leukemia (38.5%). After a median follow-up of 5.6 years, no patient with cutaneous mastocytosis had died, but 2.6% of the patients with mastocytosis in the skin, 5.7% of the patients with SM with skin involvement, and 28.95% of the patients with SM without skin involvement had died. Overall survival was longer in patients with skin involvement (cutaneous mastocytosis and/or mastocytosis in the skin and/or SM with skin involvement) than in patients with SM without skin involvement (P < 0.0001). These data argue for a thorough examination of both the skin and bone marrow in adult patients with mastocytosis.

International prognostic scoring system for mastocytosis (IPSM): a retrospective cohort study.

BACKGROUND: The WHO classification separates mastocytosis into distinct variants, but prognostication remains a clinical challenge. The aim of this study was to improve prognostication for patients with mastocytosis. METHODS: We analysed data of the registry of the European Competence Network on Mastocytosis including 1639 patients (age 17-90 years) diagnosed with mastocytosis according to WHO criteria between Jan 12, 1978, and March 16, 2017. Univariate and multivariate analyses with Cox regression were applied to identify prognostic variables predicting survival outcomes and to establish a prognostic score. We validated this International Prognostic Scoring System in Mastocytosis (IPSM) with data of 462 patients (age 17-79 years) from the Spanish network Red Española de Mastocitosis diagnosed between Jan 22, 1998, and Nov 2, 2017. FINDINGS: The prognostic value of the WHO classification was confirmed in our study (p<0·0001). For patients with non-advanced mastocytosis (n=1380), we identified age 60 years or older (HR 10·75, 95% CI 5·68-20·32) and a concentration of alkaline phosphatase 100 U/L or higher (2·91, 1·60-5·30) as additional independent prognostic variables for overall survival. The resulting scoring system divided patients with non-advanced mastocytosis into three groups: low (no risk factors), intermediate 1 (one risk factor), and intermediate 2 (two risk factors). Overall survival and progression-free survival differed significantly among these groups (p<0·0001). In patients with advanced mastocytosis (n=259), age 60 years or older (HR 2·14, 95% CI 1·42-3·22), a concentration of tryptase 125 ng/mL or higher (1·81, 1·20-2·75), a leukocyte count of 16 × 109 per L or higher (1·88, 1·27-2·79), haemoglobin of 11 g/dL or lower (1·71, 1·13-2·57), a platelet count of 100 × 109 per L or lower (1·63, 1·13-2·34), and skin involvement (0·46, 0·30-0·69) were prognostic variables. Based on these variables, a separate score for advanced mastocytosis with four risk categories was established, with significantly different outcomes for overall survival and progression-free survival (p<0·0001). The prognostic value of both scores was confirmed in 413 patients with non-advanced disease and 49 with advanced mastocytosis from the validation cohort. INTERPRETATION: The IPSM scores for patients with non-advanced and advanced mastocytosis can be used to predict survival outcomes and guide treatment decisions. However, the predictive value of the IPSM needs to be confirmed in forthcoming trials. FUNDING: Austrian Science Fund, Deutsche Forschungsgemeinschaft, Koeln Fortune Program, Charles and Ann Johnson Foundation, Instituto de Salud Carlos III, Fondos FEDER, Research-Foundation Flanders/Fonds Wetenschappelijk Onderzoek, Clinical Research-Fund of the University Hospitals Leuven, and Research-Foundation Flanders/Fonds Wetenschappelijk Onderzoek.

Vasoactive Therapy in Systemic Sclerosis: Real-life Therapeutic Practice in More Than 3000 Patients.

OBJECTIVE: Vasculopathy is a key factor in the pathophysiology of systemic sclerosis (SSc) and the main cause for Raynaud phenomenon (RP), digital ulcers (DU), and/or pulmonary arterial hypertension (PAH). It is so far unknown how patients with SSc are treated with vasoactive agents in daily practice. To determine to which extent patients with SSc were treated with different vasoactive agents, we used data from the German Network for Systemic Scleroderma registry. METHODS: The data of 3248 patients with SSc were analyzed. RESULTS: Patients were treated with vasoactive drugs in 61.1% of cases (1984/3248). Of these, 47.6% received calcium channel inhibitors, followed by 34.2% treated with angiotensin-converting enzyme (ACE) inhibitors, 21.1% treated with intravenous (IV) prostanoids, 10.1% with pentoxifylline, 8.8% with angiotensin 1 receptor antagonists (AT1RA), 8.7% with endothelin 1 receptor antagonists (ET1RA), 4.1% with phosphodiesterase type 5 (PDE5) inhibitors, and 5.3% with others. Patients with RP received vasoactive therapy in 63.3% of cases, with DU in 70.1%, and with PAH in 78.2% of cases. Logistic regression analysis revealed that patients with PAH were significantly more often treated with PDE5 inhibitors and ET1RA, and those with DU with ET1RA and IV prostanoids. In addition, 41.8% of patients were treated with ACE inhibitors and/or AT1RA. Patients registered after 2009 received significantly more often ET1RA, AT1RA, and IV prostanoids compared with patients registered prior to 2005. CONCLUSION: These data clearly indicate that many patients with SSc do not yet receive sufficient vasoactive therapy. Further, in recent years, a marked change of treatment regimens can be observed.

Impaired quality of life in patients with systemic sclerosis compared to the general population and chronic dermatoses.

BACKGROUND: Systemic sclerosis (SSc) is a rare and potentially life threatening autoimmune disorder. The burden of disease compared to other dermatoses is unknown. The purpose of this study was to assess both the quality of life in patients with SSc and the variables that are associated with poor quality of life. Forty-one patients with systemic sclerosis (29 limited, 2 diffuse, 10 undifferentiated forms) were assessed with respect to their health status and compared to published data for the normal population, SSc patients from other studies, and patients with chronic skin diseases. RESULTS: For the most part, our SSc patients had better outcomes in all 8 dimensions of the SF-36 than SSc patients from other studies, and poorer scores than the healthy population and those with occupational contact dermatitis, ichthyosis, non-melanoma skin cancer, contact dermatitis, atopic eczema, chronic nail disease, vitiligo, health care workers with work-related disease, and those with other chronic skin diseases, but significantly better scores for mental health than those with nail disease, vitiligo, and health-care workers. Patients with atopic dermatitis, psoriasis and pemphigus had significantly poorer mean scores in social function and mental health than SSc patients. Patients with pemphigus were also significantly impaired in their physical and emotional roles. Patients with systemic lupus erythematosus (SLE) had the significantly poorest mean scores for QoL in all 8 domains except bodily pain and emotional role. CONCLUSION: Besides SLE, SSc is one of the most severe chronic dermatologic diseases in terms of reduced QoL. Since SSc cannot be cured, treatment strategies should include therapeutic interventions such as psychotherapy, social support, physiotherapy, and spiritual care. Their beneficial effects could be studied in future.