Urticaria Pigmentosa Lesions Research Articles

External beam radiation therapy evaluated in patients with breast cancer with cutaneous mastocytosis.

95 Background: Mastocytosis is a rare disease characterized by an excess of mast cells. The most common presentation is cutaneous mastocytosis (CM) presenting with skin lesions of urticaria pigmentosa (UP). There is concern of anaphylactic shock from the interaction of ionizing therapeutic radiation and mast cell activation in these patients. There is very little if anything published regarding radiation treatment of patients with cutaneous mastocytosis. Literature has ranged from radiation possibly causing mastocytosis in breast cancer patients to radiation treating canine mast cell tumors. Two patients are reported in order to explore and document the tolerance and safety of breast radiation in patients with cutaneous mastocytosis. Methods: Two patients with CM presented with early stage breast cancer for radiation treatment. Three dimensional conformal radiation to the breast was given. Epinephrine injection was kept at the patient’s side during treatment. With the initiation of radiation, a steroid and additional anti-inflammatory medicine or antihistamine were taken with the baseline medication, prior to each treatment. Monitoring was performed after treatment. To minimize potential toxicity, radiation started with the boost field to confirm acceptable tolerance. Results: Both patients tolerated the radiation without any unusual acute or late toxicities. There was no anaphylaxis. Both patients showed a decrease in the UP rash in the radiated field. Tryptase levels, a marker for CM, remained stable or decreased. Conclusions: Two patients with cutaneous mastocytosis showed excellent tolerance of breast radiation therapy. In the radiation field, UP improved and may be indicative of mast cells being sensitive to radiation in small volumes. Breast radiation avoids more extensive surgery and anesthesia, which are known to exacerbate CM. Radiation therapy to the breast appears to be safe for patients with cutaneous mastocytosis. Precautions of starting with the boost field, monitoring the patients, and maximizing medical treatment, should be taken given the limited data. This report is the first to document the safety of breast radiation in patients with cutaneous mastocytosis.

Combined central xanthomatous and peripheral macular skin lesions in an infant

Combined central xanthomatous and peripheral macular skin lesions in an infant

Mastocytosis presenting as cardiac emergency

Mastocytosis is characterised by clonal proliferation of mast cells in the skin and in various internal organs, and by symptoms related to an acute release of mast cell-derived mediators. In 20-30% of patients, mastocytosis occurs without the typical skin lesions of urticaria pigmentosa that are usually the first clinical sign of the disease. In these patients, anaphylaxis is often the presenting sign of the disease. We report three cases in which a cardiac emergency (cardiac arrest or ventricular fibrillation) was the first clinical manifestation of anaphylaxis associated with systemic mastocytosis. All patients were men, none of them had previous episodes of anaphylaxis or other mediator-related symptoms, and none had major pre-existing cardiovascular condition. An eliciting factor was identified in one case (a wasp sting), but one was found in the other two. Elevation of the serum tryptase suggested a mastocytosis, which was confirmed by bone marrow biopsy. This case series demonstrates that cardiovascular emergencies may be presenting signs of mastocytosis, and that elevation of serum tryptase after an acute cardiac event, if confirmed under basal conditions, may be useful for diagnosing this disease.

Adult urticaria pigmentosa with transitory disappearance of lesions during enoxaparinum treatment

Lab A complete blood count, basic metabolic profile, hepatic and lipid panels were within normal limits and we excluded systemic involvement. A bone density study showed osteoporosis. Serum tryptase levels, 24 hour urinary N-methylhistamine, N-methylimidazoleacetic acid and prostaglandin D2 metabolites excretion werewithin normal limits. Skin biopsy cofirmed the diagnosis of generalized cutaneous mastocytosis (Urticaria pigmentosa) (Fig. 2A-D). The patient left the Dermatology Unit with no medication, but she called us, a few weeks later for a new appointment. She described and we confirmed the dissapearance of the cutaneous lesions during the last weeks, while she was hospitalised for a hip fracture and treated with Enoxaparinum 40mg s.c/daily for 14 days. The patient refused a new biopsy and we saw her again three months later, she again showed the characteristic brownishred skin lesions of Urticaria pigmentosa, exactly as at the first appointment. The lesions had begun to appear very soon after she had stopped taking Enoxaparinum (Fig. 3). ADULT URTICARIA PIGMENTOSA WITH TRANSITORY DISAPPEARANCE OF LESIONS DURING ENOXAPARINUM TREATMENT

Guías clínicas para el diagnóstico, tratamiento y seguimiento de las mastocitosis

Mastocytosis consists of a group of disorders characterized by a pathologicincrease in mast cells in tissues including skin, bone marrow, liver, spleen, andlymph nodes. Mastocytosis is a rare disease and general practitioners have limited exposure to its clinical manifestations, diagnosis, classification, and management. Moreover a complete and clear review in this field is not easy founded. Diagnosis of mastocytosis is suspected on clinical grounds and is established by histopathologic examination of involved tissues such as skin and bone marrow. The most common clinical sign of mastocytosis is the presence of typical skin lesions of urticaria pigmentosa. Most patients experience symptoms related to mast cell mediator release, and prevention of the effects of these mediators on tissues constitutes the major therapeutic goal in the management of mastocytosis. Despite recent advances in knowledge about the pathophysiology, diagnosis, and classification of mastocytosis, a curative treatment for mastocytosis does not now exist; furthermore mastocytosis is a chronic diseases with different severity grades but in all of them with an important negative impact on quality of live of patients. Management of patients within all categories of mastocytosis includes: 1. A careful counselling of patients (parents in paediatric cases) and care providers. 2. Avoidance of factors triggering acute mediator release. 3. Treatment of acute mast cell mediator release. 4. Treatment of chronic mast cell mediator release, and if indicated. 5. An attempt to treat organ infiltration by mast cells. The goal of this review is to provide a practical guide focus on diagnostic criteria for the different treatment options currently available and their management.

Anaphylaxis in patients with mastocytosis: a study on history, clinical features and risk factors in 120 patients

Excessive mast cell mediator release may lead to anaphylaxis in patients with mastocytosis. However, the incidence, clinical features and trigger factors have not yet been analyzed. To identify risk factors for anaphylaxis in mastocytosis, we determined cumulative incidence, severity, clinical characteristics, and trigger factors for anaphylaxis in 120 consecutive patients (53 male; 67 female, median age and range 24 years, 1 month to 73 years), and correlated these with disease severity of mastocytosis, skin involvement, basal total serum tryptase, and diaminooxidase concentrations. The cumulative incidence of anaphylaxis in patients with mastocytosis was higher in adults (49%; P < 0.01) compared with that in children (9%). Only children with extensive skin involvement had experienced anaphylaxis. In adults, anaphylaxis was correlated to the absence of urticaria pigmentosa lesions (P < 0.03). Reactions occurred more frequently in adults with systemic (56%) when compared with cutaneous mastocytosis (13%; P < 0.02). In adults, 48% of reactions were severe, and 38% resulted in unconsciousness. Major perceived trigger factors for adults were hymenoptera stings (19%), foods (16%), and medication (9%); however, in 26% of reactions, only a combination of different triggers preceded anaphylaxis. Trigger factors remained unidentified in 67% of reactions in children compared with 13% in adults. Patients with anaphylaxis had higher basal tryptase values (60.2 +/- 55 ng/ml, P < 0.0001) in comparison with those without (21.2 +/- 33 ng/ml), but not diaminooxidase levels. Adult patients and children with extensive skin disease with mastocytosis have an increased risk to develop severe anaphylaxis; thus, an emergency set of medication including epinephrine is recommended.

Treatment of urticaria pigmentosa using interferon alpha.

Long-term treatment with interferon alpha (IFN-alpha) has recently been shown to reduce the bone marrow infiltrate and cutaneous lesions in systemic mast cell disease. We therefore administered this cytokine to six patients with urticaria pigmentosa for up to 12 months, using subcutaneous injections of 5 x 10(6) U, initially five times, and subsequently three times a week. The generally well-tolerated therapy resulted in marked improvement of the cutaneous symptoms, especially in three of the patients who suffered from very severe pruritus. Two of the patients with bone marrow infiltration showed normal findings after treatment. However, in none of the patients was there any change in the skin lesions, or decrease in the degree of cutaneous mast cell infiltration, as evidenced by light and electron microscopic examination. These findings indicate that IFN-alpha is highly effective in the control of symptoms, but otherwise does not influence the cutaneous lesions of urticaria pigmentosa.

Successful treatment of systemic mastocytosis with high dose interferon alfa: Long-term follow-up of a case

Rationale Interferon alfa-2b (IFN-a) has been used to treat systemic mastocytosis for over 10 years. The dosage used, frequency of administration, and responses to therapy have varied widely in reported series. Here we report sustained response to high dose IFN-a given for 5 years. Methods A 44 year-old man with urticaria pigmentosa developed weight loss, anemia and leukocytosis. Bone marrow biopsy was positive for mastocytosis with 50% involvement by mast cells. Treatment was begun with IFN-a 6 million units (MU) subcutaneously 3 times/week and prednisone 10 mg on the alternate days. After 4 weeks the dose of IFN-a was increased to 10 MU 3 times/week and the dose of prednisone was tapered and discontinued. Treatment with IFN-a 10 MU 3x/week continued for the next 5 years. Results The patient re-gained his weight loss and the urticaria pigmentosa lesions faded and disappeared over 2-3 years. During 5 years of treatment the following biochemical improvements were observed: normal (initial value–> present value): Tryptase <11.5 ng/ml (>200–>37); Calcitonin 0-15.9 pg/ml (15–>9.3); Urinary prostaglandin F2a </=1000 ng/24 hr (2869–>807); Urinary N-methyl histamine 30-200 ug/g Cr. (1038–>262). Repeat bone marrow biopsy was negative for mastocytosis, and immunophenotyping of bone marrow cells was normal. Side effects included mild depression and biochemical hypothyroidism treated with levothyroxine. Conclusions For this patient, chronic treatment with IFN-a 10 MU 3x/wk, a dose higher than commonly used in other series, led to continued clinical and biochemical improvement. High-dose, prolonged treatment with IFN-a should be considered a treatment option for patients with systemic mastocytosis.

Mastocytosis: current concepts in diagnosis and treatment.

Mastocytosis consists of a group of disorders characterized by a pathologic increase in mast cells in tissues including skin, bone marrow, liver, spleen, and lymph nodes. Mastocytosis is a rare disease. Because of this, general practitioners have limited exposure to its clinical manifestations, diagnosis, classification, and management. Diagnosis of mastocytosis is suspected on clinical grounds and is established by histopathologic examination of involved tissues such as skin and bone marrow. The most common clinical sign of mastocytosis is the presence of typical skin lesions of urticaria pigmentosa. Most patients experience symptoms related to mast cell mediator release, and prevention of the effects of these mediators on tissues constitutes the major therapeutic goal in the management of mastocytosis. Despite recent advances in knowledge about the pathophysiology, diagnosis, and classification of mastocytosis, a curative treatment for mastocytosis does not now exist. Management of patients within all categories of mastocytosis includes: (1) a careful counseling of patients (parents in pediatric cases) and care providers, (2) avoidance of factors triggering acute mediator release, (3) treatment of acute mast cell mediator release, (4) treatment of chronic mast cell mediator release, and if indicated (5) an attempt to treat organ infiltration by mast cells. The goal of this manuscript is to provide an overview of the mediators produced and released by mast cells, the diagnostic criteria for the different variants of mastocytosis, and the treatment options currently available.

Occult cutaneous mastocytosis

Mastocytosis is diagnosed without difficulty if it presents with easily recognizable lesions of urticaria pigmentosa. Recently, we have identified hardly visible skin lesions of mastocytosis in Hymenoptera venom allergic patients ("occult mastocytosis"). In addition, in approximately 15% of the patients with typical cutaneous lesions, urticaria pigmentosa was at first mistaken for other conditions and thus not linked to simultaneous symptoms of systemic mastocytosis. In most patients with unrecognized mastocytosis, the diagnosis was supported by raised basal serum tryptase levels. Cutaneous mastocytosis is often overlooked and more frequent than assumed. Measurement of basal serum tryptase concentrations can make an important contribution to the diagnosis of mastocytosis, but it does not replace a meticulous skin examination.

Effects of Skin Mast Cells on Bleeding Time and Coagulation Activation at the Site of Platelet Plug Formation

We studied the effects of stimulated skin mast cells on bleeding time and thrombin generation which was measured using prothrombin fragment F 1+2 (F 1+2) and thrombin-antithrombin-III-complex (TAT). In 10 patients with urticaria pigmentosa (chronic cutaneous mast cell accumulation) the mean bleeding time was significantly prolonged in wounds made on urticaria pigmentosa lesions vs. normal skin (460 +/- 34 vs. 342 +/- 27 s, p = 0.005). In 10 atopic subjects skin incisions were made on prick-tested sites 30, 60, 120 and 240 min after administration of an allergen (acute mast cell stimulation), histamine or vehicle. The mean bleeding time was significantly prolonged at all time points, being maximal at 120 min (60% prolonged) in wounds made on allergen-stimulated skin areas (p < 0.01) compared with histamine or vehicle sites. Administration of allergen or histamine lowered the TAT concentration in the bleeding-time blood. Furthermore, TAT and F 1+2 levels in the bleeding-time blood were lower at 60, 120 and 240 min after allergen or histamine application in comparison with samples collected at 30 min. We conclude that skin mast cells can regulate primary hemostasis by prolonging bleeding time and by inhibiting thrombin generation.

Two novel mast cell phenotypic markers, monoclonal antibodies Ki-MC1 and Ki-M1P, identify distinct mast cell subtypes.

In order to identify more specific or selective mast cell markers, the reactivity of two monoclonal antibodies, Ki-MC1 and Ki-M1P, was studied by immunohistochemistry in two human cell lines (mast cell line HMC-1, basophilic cell line KU812), in mast cells cultured from blood precursors, in adherent mononuclear cells from peripheral blood, and in mast cells of tissue sections from 13 urticaria pigmentosa lesions, five mastocytomas and five normal skin specimens. Toluidine blue staining, fluorescence staining with FITC-conjugated avidin, and immunohistochemical staining (APAAP) with other mast cell reactive monoclonal antibodies, was performed for comparison. Double staining with the APAAP method, using the Ki-antibodies and toluidine blue, was also carried out. Both Ki-antibodies showed reactivity for skin mast cells, but with a different staining pattern. In addition, the Ki-MC1 antibody did not react with the cell lines, and reacted only with a few peripheral blood mononuclear cells and cultured mast cells. In contrast, the Ki-M1P antibody reacted with almost all cultured mast cells and blood mononuclear cells, but stained only about one-half of lesional and one-fifth of normal skin mast cells. Ki-M1P also reacted with many toluidine blue-negative dermal cells, particularly in urticaria pigmentosa. Ki-MC1 antibody can thus be considered as a useful additional marker for normal skin mast cells. In contrast, the Ki-M1P antibody primarily identifies immature mast cells and monocytes/macrophages, suggesting that these cell types probably originate from the same bone marrow precursor.

Expression of stem cell factor in cutaneous mastocytosis

Stem cell factor has recently been identified as a potent growth factor for bone marrow stem cells, melanocytes and mast cells. In order to evaluate its possible role in human mastocytosis, skin lesions from 13 patients with urticaria pigmentosa and five patients with mastocytomas, and normal skin specimens from five healthy donors were studied by immunohistochemistry, using polyclonal and monoclonal (hkl-12) antibodies against stem cell factor, and a monoclonal antibody (YB5.B8) against its receptor, the c-kit proto-oncogene product. Stem cell factor expression was noted in all sections studied, with an equal distribution pattern for both antibodies, but a weaker intensity with the hkl-12 reagent. Cytoplasmic staining was noted in keratinocytes, Langerhans cells, sweat gland ductal lining cells, mast cells, endothelial cells and spindle-shaped dermal stromal cells. An intense, diffusely granular reaction pattern was noted in all cells, except for a sparse, coarsely granular pattern in mast cells and stromal cells. In urticaria pigmentosa, staining was weaker in keratinocytes, but more prominent in Langerhans cells. In all sections, toluidine blue-positive mast cells and TA 99-positive basal epidermal melanocytes were the only cells to react with the c-kit antibody. Mastocytomas and urticaria pigmentosa lesions thus exhibit different patterns of stem cell factor expression. However, a possible pathogenetic role of this factor in mastocytosis remains to be determined.

Phenotypic characterization of skin lesions in urticaria pigmentosa and mastocytomas.

In order to identify possible cellular abnormalities in human mastocytosis, sections from 13 urticaria pigmentosa lesions and 5 mastocytomas were compared with 5 normal skin specimens using histochemical, enzyme histochemical and immunohistochemical techniques. All toluidine blue-positive mast cells also reacted with Fc epsilon RI and c-kit antibodies, almost all stained for tryptase, many for chymase and the myeloid workshop mast cell antibodies, few for Fc epsilon RII and none for the proliferation marker Ki-67. Urticaria pigmentosa lesions contained fewer epidermal Langerhans cells and a lower percentage of avidin-positive mast cells than mastocytomas and normal skin. Mastocytomas exhibited generally weaker staining for mast cell markers and mostly lacked Fc epsilon RI-bound IgE on mast cells and Langerhans cells, although the receptor was able to bind IgE in tissue sections. Most of the mast cell antibodies also reacted with other cell types. Only toluidine blue, avidin, tryptase and chymase stains were mast cell specific. Mast cells in mastocytosis thus differed only to a minor degree from normal mast cells, although distinct pathomechanisms may play a role in urticaria pigmentosa and mastocytosis.

Determination of the primary structures of human skin chymase and cathepsin G from cutaneous mast cells of urticaria pigmentosa lesions.

This study establishes the primary structure of human skin chymase and provides further evidence for the presence of a cathepsin G-like proteinase within human mast cells. The amino acid sequence of human skin chymase was established by protein methods and by analysis of PCR amplification products obtained with cDNA-derived from urticaria pigmentosa (UP) lesions. UP is a disease characterized by skin lesions containing high numbers of mast cells. Proteolytic digests of human chymase purified from normal skin yielded 10 resolvable peptides that were sequenced by automated Edman degradation. The amino acid sequences for these peptides combined with the sequence obtained for the protein's NH2-terminal region (35 residues) accounted for 137 residues of the human skin chymase sequence. This partial amino acid sequence corresponded to the sequence of human heart chymase, a proteinase isolated from heart tissue with immunologic and hydrolytic properties similar to skin chymase. PCR amplification of UP-derived cDNA with primers based on the cDNA structure of heart chymase demonstrated a single amplification product of expected size which was subcloned and sequenced. The amino acid sequence (135 residues) deduced from this product was identical to that of heart chymase in the region between the primers. This sequence, along with that established for the purified protein, constituted 99% of the heart chymase primary structure, strongly indicating that human skin and heart chymases have identical primary structures. Amplification of the same UP-cDNA with primers coding for the NH2- and COOH-terminal sequences of human neutrophil cathepsin G also produced a specific amplification product which was sequenced. The deduced amino acid sequence between the primers was identical to that reported for neutrophil cathepsin G, indicating that the protein of cutaneous mast cells previously shown to be immunologically cross-reactive with neutrophil cathepsin G has a comparable amino acid sequence. UP-cDNA demonstrating amplification products for cathepsin G did not demonstrate amplification products for human neutrophil elastase, suggesting that the cathepsin G PCR amplification product was not derived from neutrophils or monocytes possibly contaminating the lesion. These studies provide further evidence that human skin mast cells contain two different chymotrypsin-like proteinases.

Histamine stimulates normal human melanocytes in vitro: one of the possible inducers of hyperpigmentation in urticaria pigmentosa

Isolated normal human melanocytes became enlarged and more dendritic in association with an increase in the activity of tyrosinase and the amount of b-locus protein when they were cultured with 0.1–10 μM histamine in vitro. However, histamine did not exert a proliferative effect on them. The stimulatory effect of histamine was observable even 6 h after starting the treatment. This stimulation seems not to be pharmacologically mediated through histamine receptors, because it was inhibited neither by pyrilamine, a histamine H-1 antagonist, nor by cimetidine, a H-2 antagonist. Imidazole derivatives that are rapidly metabolized from histamine in vivo and in vitro also stimulated the melanocytes. We propose that high dermal concentrations of histamine and its imidazole metabolites continuously produced in the lesions of urticaria pigmentosa are probable causative factors of its characteristic skin pigmentation.

Lymph node findings in generalized mastocytosis.

Lymph nodes from 21 cases of generalized mastocytosis were studied histologically to confirm or exclude mast cell infiltration, and to investigate their micro-architecture. Mast cell infiltrates were detected in 17 (80%) of the lymph nodes and were found mainly in the medullary cords and sinuses. Diffuse infiltration was seen in 14 cases and focal infiltration in three cases. The following pathological findings were frequently observed: germinal centre hyperplasia (n = 14), which is probably a nonspecific finding; and hyperplasia of small blood vessels, which sometimes resembled high endothelial venules (14), eosinophilia (8), plasmacytosis (7) and collagen fibrosis (6), all of which may well be related to the effects of mediators released by mast cells. Infiltrates of acute or chronic myeloid leukaemia were seen in six lymph nodes. Division of the cases into two prognostically different groups, i.e. systemic mastocytosis, in which the skin lesions of urticaria pigmentosa are present and the prognosis is favourable, and malignant mastocytosis, in which there is no cutaneous involvement and the prognosis is poor, revealed that all six lymph nodes exhibiting leukaemic infiltrates came from the malignant mastocytosis group; eosinophilia, plasmacytosis and fibrosis were seen significantly more often in malignant than in systemic mastocytosis, but blood vessel hyperplasia and germinal centre hyperplasia were encountered with the same high frequency in both groups; and mast cell atypia tended to be more pronounced in malignant mastocytosis; this diagnosis could therefore easily be missed without naphthol AS-D chloroacetate esterase staining.(ABSTRACT TRUNCATED AT 250 WORDS)

Spleen findings in generalized mastocytosis. A clinicopathologic study.

Little information regarding the morphologic findings of the spleen in generalized mastocytosis (GM) is available and no comprehensive review of the literature on this subject has been published. The authors reviewed their records to study the macroscopic and microscopic features of the spleen in 53 patients; the authors also studied these features in 135 patients reported in the literature. Thus, a total of 188 patients with GM were studied. Splenomegaly was noted in 72% of the patients, including 71% of the patients from the authors' files and 73% of the patients reported in the literature. The spleen weight, recorded in 39 of the patients, ranged from 160 g to 2300 g; in 29 (80%) patients the spleen weighed more than 500 g and in 4 (10%) patients, more than 2000 g. However, mast cell (MC) infiltration of the spleen was recorded in only 65 (34%) patients (patients from authors' records, 39%; patients reported in literature, 32%). The following combinations were extremely rare: splenomegaly without evidence of MC infiltration (n = 1); and histologic evidence of MC infiltration in the absence of splenomegaly (n = 2). The histologic findings of the spleen could be assessed in nine of the patients from the authors' files, eight of whom had MC infiltration. In four patients, infiltration was diffuse and confined mainly to the red pulp; in the other four patients, it was more focal and involved mainly the white pulp. Spleen plasmacytosis was found in eight patients, eosinophilia in five, hemosiderosis in seven, and fibrosis in six. Concurrent acute nonlymphoblastic leukemia was diagnosed in four patients, none of whom had the skin lesions of urticaria pigmentosa. The authors' findings show that (1) splenomegaly is a common finding in GM and often is pronounced; (2) MC infiltration probably is the most important factor in the pathogenesis of splenomegaly in this disease; and (3) two different patterns of MC infiltration (diffuse and focal) can be identified in GM.

Lectin binding patterns of human tissue mast cells indicate marked phenotypical diversity

Glycoconjugate expression by human tissue mast cells (MCs) from various sources (including lymph nodes with signs of chronic non-specific lymphadenitis, skin lesions of urticaria pigmentosa, and bone marrow infiltrates associated with systemic mastocytosis) was studied histochemically with a broad panel of fluorescein-labelled lectins. Of the 19 lectins applied, 11 (sugar specificities: fucose, N-acetylgalactosamine and neuraminic acid) did not stain any MCs, while 8 (sugar specificities: mannose, N-acetylglucosamine, and galactose) were found to bind to MCs. These lectins exhibited different binding patterns in various disease entities. Only a few of these 8 lectins (in particular, phythaemagglutinin-L) produced strong staining of the MCs in most or all of the cases. Some (e. g. phythemagglutinin-E) produced only weak staining, and this in only a few cases. The lectins used, however, did not distinguish between reactive and tumorous MCs. Although lectins are therefore unlikely to be of use in resolving problems of differential diagnosis concerning proliferation of MCs, our investigation has shown that tissue MCs exhibit marked phenotypical diversity with regard to their lectin-binding properties.

Familial Urticaria Pigmentosa

We describe urticaria pigmentosa in three generations of a kindred. Unique to this family is the marked diversity of their skin disease. Classic lesions of urticaria pigmentosa, telangiectasia macularis eruptiva perstans, and clinically normal skin with positive dermal infiltrates of excess mast cells were found in individual family members. Urticaria pigmentosa is rarely reported as an inherited disease. To our knowledge, this is the largest American kindred of familial mast cell disease and is the second report documenting disease in three generations.