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There is some evidence that mastocytosis patients are at increased risk of skin cancer. This study aimed to assess the risk of malignant melanoma (MM), melanoma in situ (Mis), and basal cell carcinoma (BCC). A dataset was generated by individual-level record linkages between Swedish population registers including the National Patient Register (NPR), the Swedish Cancer Register (SCR), and the Population Register (PR). Adult patients with a mastocytosis diagnosis between 2001 and 2018 were identified in the SCR and NPR. For each case, 5 mastocytosis-free comparators matched on age, sex, and county of residence were randomly chosen from the PR. Records of skin cancer were identified in the SCR and NPR. In total, the study encompassed 2,040 mastocytosis patients of whom 63 had a record of MM/Mis and 168 a record of BCC. Compared with comparators, the risk of MM/Mis was more than twofold higher (OR 2.39, 95% CI 1.8-3.2). Risk estimates for BCC were also elevated (OR 1.77, 95% CI 1.49-2.14). When assessing the timing of skin cancers, a substantial portion were diagnosed near index date. Taken together, in the present study these findings of increased risk of MM/Mis and BCC in mastocytosis patients may reflect an influence of detection bias.

Mastocytosis is a condition characterized by the accumulation of aberrant clonal mast cells in different organs and mediator related symptoms. It is divided into two major categories, cutaneous mastocytosis and systemic mastocytosis, with subtypes ranging from indolent to aggressive forms. Although mastocytosis is considered an uncommon condition, its epidemiology has for a long time been incompletely understood, as have several aspects of comorbidity in mastocytosis patients.

Paper I aimed to investigate the epidemiology of mastocytosis by estimating the incidence, prevalence and overall survival, and the comorbidity burden between individuals with mastocytosis and comparators using data from Swedish national registers. This population-based study found an annual incidence of 1.56 per 100,000 and a prevalence of 23.9 per 100,000, exceeding previous estimates from other studies. The comorbidity burden was higher in the mastocytosis patients, compared to comparators. We confirmed that the prognosis generally is favorable, but with marked survival differences between subtypes.

Paper II aimed to examine whether mastocytosis patients are at an increased risk of developing malignant melanoma (MM), melanoma in situ (MIS) or basal cell carcinoma (BCC) compared to the background population. By merging data from several Swedish population-based registries we found that patients with mastocytosis were at a more than two-fold higher risk for MM and MIS. The risk estimates for BCC were also elevated. We also found that a substantial portion of skin cancers were diagnosed near index date, suggesting a possible influence of detection bias.

Paper III further evaluated the risk of skin cancer through a large-scale, retrospective, propensity-score-matched cohort study utilizing data in a large U.S. healthcare database. We found that mastocytosis patients had significantly elevated lifetime risks of all skin cancers compared to comparators. Sensitivity analyses designed to assess detection bias indicated that detection bias alone cannot fully explain the increased risk of skin cancers in mastocytosis patients.

In conclusion, we found higher incidence and prevalence of mastocytosis than previously reported, along with evidence of a higher comorbidity burden. Additionally, our data suggest that patients with mastocytosis are at an increased risk of being diagnosed with skin cancer, warranting heightened dermatological surveillance.

Background: Mastocytosis is a disease characterized by accumulation of aberrant mast cells and mediator-related symptoms and is divided into systemic mastocytosis (SM) and cutaneous mastocytosis (CM). The epidemiology of mastocytosis remains incompletely understood. Objective: To estimate the incidence, prevalence, overall survival (OS) and burden of comorbidities in adult mastocytosis patients identified in Swedish population-based registries. Methods: Individuals (>= 20 years of age) with a mastocytosis diagnosis in the National Patient Register (NPR) and/or the Swedish Cancer Register (SCR) between 2001 and 2018, were identified. In a matched cohort design, for each case five randomly selected mastocytosis-free comparators matched on age, sex, and county of residence were chosen from the Population Register. The Kaplan-Meier method was used to compare OS between individuals with mastocytosis and comparators. Information on concomitant disease at baseline was assessed by use of the Charlson Comorbidity Index (CCI). Results: We identified 2,040 adults with a mastocytosis diagnosis yielding an annual incidence of 1.56 per 100,000 (95% CI 1.29-1.87) and a prevalence of 23.9 per 100,000 (95% CI 22.8-25.0). The comorbidity burden was higher, and the OS lower, in patients with mastocytosis compared to comparators. Interpretation: We found a higher incidence and prevalence of mastocytosis compared to assessments in other settings and confirmed that the prognosis generally is favorable. Of special note was evidence of a higher comorbidity burden in mastocytosis patients compared to the background population. Limitations: Underreporting and inconsistencies in the use of diagnostic codes.

Mastocytosis is a KIT-related myeloproliferative disease characterised by abnormal expansion of neoplastic mast cells (MC) in the skin or virtually any other organ system. The cutaneous form of adult-onset mastocytosis is almost invariably combined with indolent systemic involvement for which curative therapy is yet not available. Here we evaluated a concept of depleting cutaneous MCs in mastocytosis lesions ex vivo by targeting their secretory granules. Skin biopsies from mastocytosis patients were incubated with or without mefloquine, an antimalarial drug known to penetrate into acidic organelles such as MC secretory granules. Mefloquine reduced the number of dermal MCs without affecting keratinocyte proliferation or epidermal gross morphology at drug concentrations up to 40 mu M. Flow cytometric analysis of purified dermal MCs showed that mefloquine-induced cell death was mainly due to apoptosis and accompanied by caspase-3 activation. However, caspase inhibition provided only partial protection against mefloquine-induced cell death, indicating predominantly caspase-independent apoptosis. Further assessments revealed that mefloquine caused an elevation of granule pH and a corresponding decrease in cytosolic pH, suggesting drug-induced granule permeabilisation. Extensive damage to the MC secretory granules was confirmed by transmission electron microscopy analysis. Further, blockade of granule acidification or serine protease activity prior to mefloquine treatment protected MCs from apoptosis, indicating that granule acidity and granule-localised serine proteases play major roles in the execution of mefloquine-induced cell death. Altogether, these findings reveal that mefloquine induces selective apoptosis of MCs by targeting their secretory granules and suggest that the drug may potentially extend its range of medical applications.

BACKGROUND: Mastocytosis in adults often presents with skin lesions. A bone marrow biopsy is necessary to confirm or exclude the presence of systemic mastocytosis (SM) in these cases. When a bone marrow biopsy is not performed, the provisional diagnosis is mastocytosis in the skin (MIS). No generally accepted scoring system has been established to estimate the risk of SM in these patients. OBJECTIVE: To develop a risk score to predict SM in adults with MIS. METHODS: We examined 1145 patients with MIS from the European Competence Network on Mastocytosis Registry who underwent a bone marrow biopsy. A total of 944 patients had SM and 201 patients had cutaneous mastocytosis; 63.7% were female, and 36.3% were male. Median age was 44 +/- 13.3 years. The median serum tryptase level amounted to 29.3 +/- 81.9 ng/mL. We established a multivariate regression model using the whole population of patients as a training and validation set (bootstrapping). A risk score was developed and validated with receiver-operating curves. RESULTS: In the multivariate model, the tryptase level (P < .001), constitutional/cardiovascular symptoms (P = .014), and bone symptoms/osteoporosis (P < .001) were independent predictors of SM (P < .001; sensitivity, 90.7%; specificity, 69.1%). A 6-point risk score was established (risk, 10.7%-98.0%) and validated. CONCLUSIONS: Using a large data set of the European Competence Network on Mastocytosis Registry, we created a risk score to predict the presence of SM in patients with MIS. Although the score will need further validation in independent cohorts, our score seems to discriminate safely between patients with SM and with pure cutaneous mastocytosis. (C) 2020 American Academy of Allergy, Asthma & Immunology

Background: Data on pregnancy outcomes in women with psoriasis are conflicting.

Objective: We examined whether maternal psoriasis affects the risk of adverse maternal and pregnancy outcomes.

Methods: We used population-based data to compare reproductive patterns in women with and without psoriasis. Odds ratios (ORs) with 95% confidence intervals (CIs) for adverse outcomes were estimated with adjustments for maternal age, period of childbirth, smoking, and prepregnancy body mass index.

Results: Compared with women without psoriasis, women with psoriasis were younger at first birth and had longer interpregnancy intervals but did not differ in final parity. Risk estimates in women with psoriasis were elevated for pregnancy hypertension (OR, 1.37; 95% CI, 1.19-1.58), premature rupture of membranes (OR, 1.15; 95% CI, 1.04-1.27), large for gestational age (OR, 1.11; 95% CI, 1.01-1.21), cleft palate (OR, 1.69; 95% CI, 1.07-2.66), and unspecified malformations (OR, 1.08; 95% CI, 1.01-1.16).

Limitations: No information was available on lifestyle, disease severity, or type and duration of treatment. Small numbers hampered the assessment of rare outcomes.

Conclusion: Although there was no evidence that fertility is negatively affected, women with psoriasis were at an increased risk of several adverse maternal and pregnancy outcomes. Our findings add to a growing body of evidence that pregnancies in women with psoriasis need special monitoring.

Mastocytosis is a heterogeneous group of diseases defined by an increased number and accumulation of mast cells, and often also by signs and symptoms of mast cell activation. Disease subtypes range from indolent to rare aggressive forms. Mastocytosis affects people of all ages and has been considered rare; however, it is probably underdiagnosed with potential severe implications. Diagnosis can be challenging and symptoms may be complex and involve multiple organ-systems. In general it is advised that patients should be referred to centres with experience in the disease offering an individualized, multidisciplinary approach. We present here consensus recommendations from a Nordic expert group for the diagnosis and general management of patients with mastocytosis.