Sustained improvement in urticaria pigmentosa and pruritus in a case of indolent systemic mastocytosis treated with cladribine.

Systemic mastocytosis (SM) is a myeloproliferative disorder, characterized by a clonal proliferation of abnormal mast cells accumulating in internal organs and sometimes in the skin, leading to cutaneous and systemic symptoms. Mutations within the gene KIT, which encodes the receptor tyrosine kinase (KIT) on mast cells, is found in most patients with SM. We report a case of a 62-year-old woman presenting with a pruritic rash on her limbs and trunk. Several years later she developed gastrointestinal symptoms, associated with raised serum tryptase. Skin and bone marrow biopsies confirmed a diagnosis of SM, initially presenting with urticaria pigmentosa. Responses to multiple therapies, including potent topical steroids, oral antihistamines, phototherapy and the tyrosine kinase inhibitor, nilotinib, were inadequate. Treatment with cladribine (2-chlorodeoxyadenosine) produced a marked and sustained reduction in her symptoms and serum tryptase level.

Urticaria pigmentosa-like disease in a dog.

Urticaria pigmentosa is a rare dermatologic syndrome in humans, cats, and dogs. This report documents a case of canine urticaria pigmentosa-like disease with unusual features and no C-kit mutation.

Maladie s'apparentant à l'urticaire pigmentaire chez un chien. L'urticaire pigmentaire est un syndrome dermatologique rare chez les humains, les chats et les chiens. Ce rapport documente un cas canin s'apparentant à l'urticaire pigmentaire comportant des caractéristiques inhabituelles et l'absence de mutation C-kit.(Traduit par Isabelle Vallières).

Cutaneous mastocytosis extending beyond a radiotherapy site: a form of radiodermatitis or a neoplastic phenomenon?

Ionising radiation is often used as an adjuvant in the management of breast cancer. Acute and chronic skin changes are well recognised complications associated with its use. We demonstrate a rare clinical presentation of cutaneous mastocytosis that occurred at the site of radiotherapy and then extended beyond this boundary, and ask whether this can be treated as a localised side effect of radiotherapy or whether the potential for systemic mastocytosis needs to be excluded.

Cutaneous mastocytosis: a case of bullous urticaria pigmentosa.

Mastocytosis is characterized by an increased number of mast cells with abnormal growth and accumulation in 1 or more organs. In children, mastocytosis is commonly cutaneous and patients present with a spectrum of findings, ranging from solitary or multiple mastocytomas to urticaria pigmentosa (UP) or diffuse cutaneous mastocytosis (CM). We present a case of a 4-month-old infant with bullous UP.

Cutaneous mastocytosis associated with congenital alopecia.

Mastocytosis is a rare disorder that shows accumulation of mast cells in tissues. Atypical clinical features may mimic impetigo, Langerhans cell histiocytosis, and carcinoid syndrome; however, only 1 case of scarring alopecia associated with mastocytosis has been reported. We present the first case of cutaneous mastocytosis associated with congenital alopecia areata in a 3-year-old Korean girl. This case showed an atypical clinical presentation of congenital alopecia areata, but histopathological results confirmed the diagnosis of cutaneous mastocytosis.

Cutaneous mastocytosis exacerbated by pinworms in a young boy.

Cutaneous mastocytosis in children has an indolent course and undergoes spontaneous regression. Many triggering factors may cause mast cell degranulation and clinical manifestations. Knowledge of these factors is important for patients and their families. We report a case of exacerbation of urticaria pigmentosa due to mast cell degranulation caused by Enterobius vermicularis, which has not been reported before as a triggering factor.

Cutaneous mastocytosis in Thai children.

BACKGROUND: Mastocytosis is a disorder of mast cells proliferation within various organs, most commonly in the skin. The disease more commonly appears during infancy than adult. OBJECTIVE: To characterize the clinical features, response to therapy and prognosis of cutaneous mastocytosis in children. MATERIAL AND METHOD: A retrospective study of cutaneous mastocytosis was performed at Queen Sirikit National Institute of Child Health during January 1994 to December 2007.All cases were confirmed by histological diagnosis. RESULTS: There were a total of 50 patients. The male to female ratio was 1:1.2. Age at onset of lesions ranged from birth to 7 years. Forty-seven patients (94%) developed skin lesions within the first year of ife. There were 45 cases (90%) of urticaria pigmentosa, 3 cases (6%) of mastocytoma and 2 cases (4%) of diffuse cutaneous mastocytosis. None of the patient had a family history of cutaneous mastocytosis. Most of the children were healthy, except the one who had germ cell ovarian tumor Skin biopsies were performed in all cases and revealed mast cells infiltrate in the dermis. Treatment included oral antihistamine in all cases. Oral mast cell stabilizers were given in 6 patients (12%) and topical corticosteroids in 15 patients (30%). Four patients (8%) were treated with oral prednisolone. The skin lesions resolved only in 1 patient (2%) at age 7.8 years, the others still had skin lesions without systemic symptoms. CONCLUSION: Cutaneous mastocytosis is a benign disease in children without systemic involvement.

Peripheral interstitial keratitis: a novel manifestation of ocular mastocytosis.

PURPOSE: To report a case of peripheral interstitial keratitis in a patient with mastocytosis. METHODS: Clinical case description and immunohistologic examination of biopsied ocular tissue. RESULTS: A 22-year-old woman with biopsy-proven urticaria pigmentosa, a subset of mastocytosis, presented with an active peripheral interstitial keratitis with vascularization associated with foreign body sensation and itching. Biomicroscopy of the cornea showed deep corneal inflammatory infiltrates and midstromal vascularization adjacent to a region of superior bulbar conjunctiva, which was mildly chemotic and inflamed. Topical mast cell stabilizers and a short course of topical steroids produced dramatic resolution of the lesion. Biopsy of the erythematous conjunctiva adjacent to the area of corneal inflammation showed the presence of mast cells. CONCLUSION: This is the first case of corneal inflammatory infiltration in a patient with mastocytosis. Therapy for this condition consists of a combination of topical mast cell stabilizers, topical steroids, and systemic antihistaminic therapy.

Cutaneous mastocytosis: report of six cases.

Cutaneous mastocytosis is a rare infiltrative disorder of the skin. Though often asymptomatic, systemic features may be associated with any clinical pattern of the disorder at any age group. We present our experience with six cases of cutaneous mastocytosis, including three with diffuse cutaneous mastocytosis, a rare entity.

Therapeutic challenge during the long-term follow-up of a patient with indolent systemic mastocytosis with extensive cutaneous involvement.

From a dermatological aspect, it posed a considerable challenge the skin-limited form of mastocytosis, urticaria pigmentosa and indolent systemic mastocytosis (ISM) with cutaneous lesions. Despite the favourable prognosis, lifelong dermatological control is needed, during which the average symptomatic therapy does not always seem adequate. We report here the case of a female ISM patient with recurrent cutaneous symptoms that impaired her quality of life, with a follow-up time of 27 years. During this long follow-up period, the cutaneous lesions could be controlled by antihistamines, leukotriene antagonists, glucocorticoids, local immunosuppressants or local UV radiation for only relatively short periods. Imatinib mesylate was, therefore, introduced in an attempt to control the cutaneous lesions. Tyrosine kinase inhibition is an unusual dermatological therapeutic option. This case illustrates that imatinib mesylate was a good choice with which to achieve a reduction of the skin lesions in this KIT D816V mutation-negative disease: it led to a temporary appreciable improvement of the patient's quality of life.

Decreased urinary histamine metabolite after successful PUVA treatment of urticaria pigmentosa.

The effect of PUVA therapy on pruritus, the skin mast cell population and histamine metabolism has been studied in 3 patients with urticaria pigmentosa and manifestations of systemic mastocytosis. Relief of itch was found concomitant with a significant decrease of the major histamine metabolite 1-methyl-4-imidazoleacetic acid in the urine. The decrease occurred during the first 2 mo after starting PUVA therapy and was sustained during an observation period of 3 mo after discontinuation of the treatment. At this time a reduction of the number of mast cells was found in skin biopsy specimens. No evidence of acute histamine release in association with PUVA treatment was obtained. These results suggest that this effective new treatment for urticaria pigmentosa reduces the histamine turnover in the skin by inhibiting mast cell proliferation.

Response of cutaneous mast cells to PUVA in patients with urticaria pigmentosa: histomorphometric, ultrastructural, and biochemical investigations.

In six patients with urticaria pigmentosa, population density and ultrastructure of the cutaneous mast cells and histamine levels of the lesional skin were studied before, immediately after, and again 5-8 months after photochemotherapy (PUVA). Immediately after PUVA, the total mast cell number was not reduced, but on separate analysis of the intradermal distribution, significantly fewer mast cells were found in the papillary dermis and correspondingly more mast cells in the adjacent upper dermis. On electron microscopic examination, 4% of the mast cell granules were immature before and 27% after PUVA therapy, based on the lower electron density of the granular matrix. This was associated with a markedly lower histamine content of the lesional skin. Five to eight months after recovery from PUVA, the morphologic changes and the histamine levels had all returned to the pre-PUVA status. These findings were paralleled by a reversal of all clinical beneficial effects that had been observed with PUVA.

Increased formation of thromboxane in vivo in humans with mastocytosis.

Clinical manifestations of mastocytosis are mediated, at least in part, by release of the mast cell mediators histamine and prostaglandin D2. It has been previously reported that in addition to prostaglandin D2, mast cells produce other eicosanoids, including thromboxane. Nonetheless, little information exists regarding the formation of other prostanoids in vivo. The most accurate method to examine the systemic production of eicosanoids in vivo is the quantitation of urinary metabolites. We previously developed a highly accurate assay employing mass spectrometry to measure a major urinary metabolite of thromboxane, 11-dehydro-thromboxane B2, in humans. We utilized this assay to quantitate thromboxane production in 17 patients with histologically proven mastocytosis. We report that thromboxane formation was significantly increased (>2 SD above the mean) in at least one urine sample from 65% of patients studied. Of these, 91% of patients with documented systemic involvement had elevated thromboxane generation. In addition, endogenous formation of thromboxane was highly correlated with the urinary excretion of the major urinary metabolite of prostaglandin D2 (r = 0.98) and Ntau-methylhistamine (r = 0.91), suggesting that the cellular source of increased thromboxane in vivo could be the mastocyte. Enhanced thromboxane formation in patients with this disorder is unlikely to be of platelet origin as other markers of platelet activation, platelet factor 4 and beta-thromboglobulin, were not increased in three patients with marked overproduction of thromboxane. Furthermore, the recovery of 11-dehydro-thromboxane B2 excretion in two patients after the administration of aspirin occurred significantly more rapidly than the recovery of platelet thromboxane generation. These studies, therefore, report that thromboxane production is significantly increased in the majority of patients with mastocytosis that we examined and provide the basis to elucidate the role of this eicosanoid in disorders of mast cell activation.

The effect of cimetidine and propantheline on the symptoms of a patient with systemic mastocytosis.

A 24 year old white woman with a lifelong history of systemic mastocytosis and symptoms of diarrhea and flushing was demonstrated to have a normal gastric analysis and inconsistent steatorrhea. She responded well to oral cimetidine therapy for 11 months. A symptomatic recurrence was controlled with the addition of propantheline. Gastric secretory studies demonstrated cimetidine suppression of both basal acid and basal pepsin secretion, as well as maximal pentagastrin-stimulated acid secretion; suppression of stimulated pepsin secretion was minimal. The combination of cimetidine and propantheline markedly suppressed both peak acid and peak pepsin secretion in response to pentagastrin stimulation. These data support a dominant role of cholinergic mechanisms in the control of gastric pepsin secretion; additional data obtained with maintenance of constant intragastric pH are required for further clarification.

Comparison of the therapeutic efficacy of cromolyn sodium with that of combined chlorpheniramine and cimetidine in systemic mastocytosis. Results of a double-blind clinical trial.

Both antihistamines and cromolyn sodium have been suggested for the treatment of systemic mastocytosis. To determine if one drug regimen was superior to the other, eight patients with systemic mastocytosis were admitted to a double-blind, double-crossover study in which the therapeutic efficacy of cromolyn sodium was compared with that of a combination of chlorpheniramine and cimetidine. Response to therapy was assessed by the patients using symptom scores and by the attending physicians during clinic examinations in addition to sequential plasma and urinary histamine determinations. In the six patients who completed the trial, the patient symptom scores and the physician evaluations indicated that there was no advantage of one drug regimen over the other. Plasma and urinary histamine levels, markedly elevated in most of the patients, were not consistently altered by administration of either cromolyn sodium or the combined antihistamines. Thus, cromolyn sodium and the combined antihistamines were indistinguishable when used for the symptomatic treatment of systemic mastocytosis, and neither regimen altered systemic histamine levels.

Comparison of the effectiveness of ranitidine and cimetidine in inhibiting acid secretion in patients with gastric hypersecretory states.

The H2-histamine receptor antagonists ranitidine and cimetidine were compared for their abilities to control gastric acid hypersecretion on a short- and long-term basis in 22 patients with gastric acid hypersecretory states. Nineteen patients had Zollinger-Ellison syndrome, one patient had systemic mastocytosis, and two patients had idiopathic hypersecretion. The rates of onset of the action of cimetidine and ranitidine were the same. The actions of both drugs were increased by anticholinergic agents, and there was a close correlation between the daily maintenance dose of each drug needed to control acid secretion. However, ranitidine was threefold more potent than cimetidine both in acute inhibition studies and in the median maintenance dose needed (1.2 g per day for ranitidine and 3.6 g per day for cimetidine). Sixty percent of the males developed breast changes or impotence while taking cimetidine and in all cases these changes disappeared when cimetidine was replaced by ranitidine. Treatment with high doses of cimetidine (one to 60 months; median, 11 months) or ranitidine (two to 31 months; median, 14 months) was not associated with hepatic or hematologic toxicity or alterations of serum gastrin concentrations, but ranitidine therapy was associated with a significantly lower serum creatinine level than seen with cimetidine therapy. The results show that both drugs can adequately inhibit acid secretion in patients with gastric hypersecretory states. Both are safe at high doses, but ranitidine is threefold more potent and does not cause the antiandrogen side effects frequently seen with high doses of cimetidine.