Telangiectasia macularis eruptiva perstans (TMEP): A form of cutaneous mastocytosis with potential systemic involvement.

BACKGROUND: Telangiectasia macularis eruptiva perstans (TMEP) has not been fully characterized. OBJECTIVE: We sought to estimate the frequency and clinical characteristics of TMEP in a cohort of adult patients with cutaneous mastocytosis, and to assess the presence of systemic involvement. METHODS: We included all consecutive patients evaluated for cutaneous mastocytosis in 2 centers: the Mastocytosis Competence Center of the Midi-Pyrénées from May 2006 to December 2013, and the French Reference Center for Mastocytosis from January 2008 to September 2013. Skin phenotype, histopathology, presence of KIT mutation in the skin, and assessment of systemic involvement according to World Health Organization (WHO) criteria were prospectively investigated. RESULTS: Of 243 patients with cutaneous mastocytosis, 34 (14%) were given a diagnosis of TMEP. The diagnosis of systemic mastocytosis was established in 16 patients (47%) with TMEP. Three patients (9%) had aggressive systemic mastocytosis (C-findings according to WHO). In all, 32 patients (94%) exhibited at least 1 mast cell activation-related symptom. LIMITATIONS: Patient recruitment was undertaken at 2 referral centers with expertise in the diagnosis and treatment of mastocytosis so that the clinical findings and incidence of systemic involvement may be overestimated in comparison with the overall population of patients with TMEP. CONCLUSION: TMEP accounts for about 14% of patients with cutaneous mastocytosis. The disease manifests as mast cell activation symptoms in almost all patients and can be associated with systemic involvement in about 50% of cases.

[Urticaria pigmentosa: a current approach]. / Urticaria pigmentosa: un enfoque actual.

The term urticaria pigmentosa (UP) denotes a heterogeneous group of disorders characterized by abnormal growth and accumulation of mast cells (MC) in the skin. Symptoms result from MC chemical mediator's release, pathologic infiltration of neoplastic MC in tissues or both. Multiple molecular, genetic and chromosomal defects seem contribute to an autonomous growth, but somatic c-kit D816V mutation is more frequently found, especially in systemic disease. The aim of this paper is to provide a current overview for a better understanding of the symptoms associated with this disease, to describe its classification, recent advances in its pathophysiology and its treatment.

[Mastocytosis--two diseases with different physiopathology]. / Mastocytos--två sjukdomar med olika patofysiologi.

Mastocytosis means proliferation and accumulation of mast cells in skin and internal organs. Bone marrow cytogenetic abnormalities are similar to those found in myeloproliferative diseases. Recent findings indicate different pathogenetic forms of mastocytosis. Thus, adult patients with associated hematological diseases express mutation of the gene for the thyrosine kinase receptor, while childhood cases lack this mutation. In adults the skin and bone marrow are the most commonly affected organs but involvement of the skeleton and gastrointestinal tract also occur. Hematological malignancy is a rare but well-recognized complication. Childhood onset mastocytosis in the skin regresses spontaneously, whereas virtually all of the adult-onset cases persist.

Regression of urticaria pigmentosa in adult patients with systemic mastocytosis: correlation with clinical patterns of disease.

OBJECTIVE: To determine clinical correlates of urticaria pigmentosa (UP) regression in adult patients with systemic mastocytosis (SM). DESIGN: Cohort study of the natural history of mastocytosis. SETTING: National Institutes of Health Clinical Center. PATIENTS: In a study of adult patients referred to the National Institutes of Health after 1980 and observed for a minimum of 10 years, 12 of 106 adult patients experienced clearance or fading of UP. MAIN OUTCOME MEASURES: Data from each patient's history and results of physical examination, laboratory evaluation, and organ biopsy at presentation to the National Institutes of Health were compared with findings at the patient's most recent visit. RESULTS: In the patients in whom clearance of (n = 5) or a decrease in skin lesions (n = 7) was noted, UP had persisted from 4 to 34 years (median, 17 years). Older age was a prognostic feature for regression of UP. Despite improvement of UP, the 2 patients with SM with an associated hematologic disorder experienced a deterioration in clinical condition. In the 10 patients with indolent SM, severity and frequency of symptoms decreased as the UP regressed. However, bone marrow changes consistent with SM remained. CONCLUSIONS: Urticaria pigmentosa regresses in approximately 10% of the older patients who have SM. In patients with an associated hematologic disorder such as myelodysplasia, this regression may be accompanied by disease progression. In contrast, regression of UP in patients with indolent SM parallels a decrease in disease intensity, although bone marrow findings of indolent SM remain.

In vitro reactivity of mast cells in urticaria pigmentosa skin.

The aim of our study was to evaluate the sensitivity of skin mast cells from urticaria pigmentosa (UP) patients to substance P (SP), tumor necrosis factor alpha (TNF-alpha) and anti-IgE, and to compare the sensitivity of these cells with that of skin mast cells from healthy human donors. Mast cells for in vitro functional studies were obtained using an enzymatic dispersion technique from skin biopsies (from 11 patients with UP and 11 healthy donors), and the reactivity of these cells was estimated on the basis of histamine release. Our observations indicated that UP skin mast cells and healthy skin mast cells had similar sensitivities to challenge with TNF-alpha at a concentration 10(-7) M (16.4% vs 15.2%) and with anti-IgE at a dilution 1:100 (41.0% vs 37.0%). However, UP mast cells showed considerably higher sensitivity to challenge with SP at a concentration 10(-4) M than healthy skin mast cells (20.0% vs 6.8%), and the difference was statistically significant (P < 0.001). UP skin mast cells also demonstrated significantly higher spontaneous histamine release than healthy skin mast cells (32.1% vs 12.4%, P < 0.001). Our findings indicating UP skin mast cell sensitivity to SP might suggest that mechanisms involving neurogenic inflammation could contribute to the course of this disease.

Mastocitosis en la edad pediátrica. Comunicación de tres casos / Mastocytosis on chioldhood: three cases report

La mastocitosis es una enfermedad que se caracteriza por un incremento en el número de mastocitos, que puede aparecer durante la edad pediátrica, clasificándose en dos grandes grupos. El primero está confirmado a la piel (mastocitosis cutánea) y el segundo involucra varios órganos 8mastocitosis sistémica). La mastocitosis cutánea generalmente se cura de manera espontánea a esta edad; sin embargo, debemos vigilar su evolución ante la posibilidad de complicaciones sistémicas. La mastocitosis sistémica es más frecuente en la edad adulta; sus síntomas son resultado de la liberación de mediadores, tales como la histamina, leucotrienos, prostaglandinas y otros. El tratamiento se dirige al control de los síntomas. Se comunican tres casos clínicos vistos en el Hospital infantil de México Federico Gómez, insistiendo en la benignidad de esta afección durante la niñez

Bone density, bone markers and bone radiological features in mastocytosis.

We examined the association between severity of disease in mastocytosis and skeletal manifestation and bone markers in 16 patients varying in extent of mastocytosis as determined by the urine excretion of methylimidazoleacetic acid. Both osteoporosis and osteosclerosis were found. Bone density in the hip was significantly higher (p < 0.05) in both men and women with an enhanced histamine metabolite excretion. Patients with only moderately increased mast cell mass had low bone mineral density in the hip, osteoporosis and vertebral fractures. The different skeletal disease patterns in mastocytosis might be the effect on osteoblasts and osteoclasts of biologically active substances. Mast cells release a number of vasoactive substances, including histamine which promotes osteoblasts and heparin and prostaglandin D2 which induce bone resorption by activation of osteoclasts. Systemic mastocytosis is a rare disease characterized by multi-organ infiltration by mast cells and with varying skeletal manifestations including osteoporosis. Treatment with bisphosphonates may be beneficial in arresting osteoporosis in this disorder.

Mastocitosis cutánea difusa, presentación de un caso y revisión del tema / Difuse cutaneous mastocytosis: report of a case

Se presenta el caso de un paciente masculino de 5 meses de edad, diagnosticado clínica e histológicamente como mastocitosis cutánea difusa, se hace una revisión del tema

Urticaria pigmentosa: a review of 67 pediatric cases.

Mastocytosis is a disorder of mast cell proliferation that may appear during infancy, childhood, or adulthood. We studied 67 consecutive patients (33 males, 34 females) with urticaria pigmentosa and assessed them fully to determine the presence of systemic involvement. Ages at onset of lesions ranged from birth to 11 years, with most developing in the first year of life. Pruritus was the primary symptom. Hematologic and serum chemistry profile, radiologic skeletal surveys, and bone marrow aspirations were performed. Slight anemia was present in three patients. Radiologic bone lesions were observed in eight. Bone marrow aspirates showed slight changes in six patients, with only an increased number of mast cells in an additional patient. The disease tended to resolve spontaneously. This prospective study emphasizes the benign nature of pediatric urticaria pigmentosa.

Continuous release of secretory granule proteoglycans from a cell strain derived from the bone marrow of a patient with diffuse cutaneous mastocytosis.

A human cell strain (designated HBM-M) that was derived from the bone marrow of a child with diffuse cutaneous mastocytosis was previously found to possess features that suggested it belonged in the mast cell/monocyte lineage. HBM-M cells synthesized approximately 150-Kd Pronase-resistant proteoglycans that were recognized by an antihuman secretory granule proteoglycan peptide core antibody. These cells also contained in relatively high abundance the same sized mRNA transcript that encodes the peptide core of proteoglycans that are normally localized to secretory granules of hematopoietic cells. However, unlike most other hematopoietic cells, HBM-M cells continuously released their newly synthesized 35S-labeled proteoglycans rather than retaining them in an intracellular storage compartment. Chondroitinase ABC, nitrous acid, and heparinase degraded approximately 76%, 17%, and 7%, respectively, of the HBM-M cell-derived 35S-labeled proteoglycans. As assessed by high performance liquid chromatography, 91% of the unsaturated 35S-labeled disaccharides generated by treatment with chondroitinase ABC were delta Di-4S. The remaining chondroitin sulfate 35S-labeled disaccharides appeared to be primarily a complex mixture of disulfated disaccharides. The 35S-labeled glycosaminoglycans that were not degraded by chondroitinase ABC migrated in two-dimensional cellulose acetate electrophoresis as if they were heparan sulfate or under-sulfated heparin. Thus, although the HBM-M cell-derived proteoglycans had some of the features of proteoglycans produced by normal human mast cells, the heparin-like and chondroitin sulfate glycosaminoglycans bound to the HBM-M cell proteoglycans were considerably less sulfated. Because the only human cell types that have so far been shown to synthesize proteoglycans that have heparin-like glycosaminoglycans bound to a protease-resistant peptide core are mast cells and basophilic leukocytes from patients with myelogenous leukemia, it is possible that the HBM-M cell is a mast cell progenitor cell.