The efficacy of omalizumab in Cutaneous Mastocytosis: A case series

Background: Mastocytosis describes a heterogeneous group of disorders arising from a clonal proliferation of mast cells. Given the lack of curative treatments for the cutaneous form, there is a significant need for superior therapies. Omalizumab is a recombinant DNA‐derived humanized IgG monoclonal antibody that selectively binds to human immunoglobulin E (IgE). It represents a potential treatment for the management of cutaneous mastocytosis, which currently has no standard treatment. Methods: Two patients were treated with subcutaneous omalizumab 300 mg every 4 weeks. Discussion: Patient 1 experienced 50% reduction in cutaneous infiltration and moderate improvement in pruritus. Patient 2 underwent 90% complete clearance of cutaneous lesions and reported full resolution of pruritus. The median duration of treatment was 24 weeks and time to response was 8 weeks. No significant changes in tryptase levels were observed. Both patients experienced injection site reactions. Conclusion: We provide evidence from two cases supporting the efficacy of IgE‐mediated therapy in the treatment of cutaneous mastocytosis. Even at a higher‐than‐standard dose (300 mg vs. 150 mg), the drug was well‐tolerated. As we await the results of pivotal clinical trials, omalizumab appears to be a promising treatment option in patients with cutaneous mastocytosis unresponsive to traditional therapies.     

Cutaneous mastocytosis: A dermatological perspective

Mastocytosis is a rare disease characterised by expansion and collection of clonal mast cells in various organs including the skin, bone marrow, spleen, lymph nodes and gastrointestinal tract. The prevalence of mastocytosis has been estimated to be one in 10 000, while the estimated incidence is one per 100 000 people per year. Cutaneous mastocytosis is classified into (i) maculopapular cutaneous mastocytosis, also known as urticaria pigmentosa; (ii) diffuse cutaneous mastocytosis; and (iii) mastocytoma of the skin. In adults, cutaneous lesions are usually associated with indolent systemic mastocytosis and have a chronic evolution. Paediatric patients, on the contrary, have often cutaneous manifestations without systemic involvement and usually experience a spontaneous regression. Diagnosis of cutaneous mastocytosis may be challenging due to the rarity of the disease and the overlap of cutaneous manifestations. This short review describes pathogenesis and clinical aspects of cutaneous mastocytosis with a focus on diagnosis and currently available therapies.     

Mastocytosis in children: a protocol for management

Abstract:  Mastocytosis is characterized by an increased number of mast cells with an abnormal growth and accumulation in one or more organs. In most children mastocytosis is limited to the skin (cutaneous mastocytosis) and often transient as compared with that in adults in whom mastocytosis is usually progressive and systemic. Generally, we recognize three more common forms of cutaneous mastocytosis: maculopapulous mastocytosis (formerly urticaria pigmentosa), mastocytoma of skin, and diffuse cutaneous mastocytosis. Childhood mastocytosis can further be divided into cutaneous mastocytosis (nonpersisting and persisting) and systemic mastocytosis (extremely rare). An approach to management using a set protocol is described in table form. In most cases of mastocytosis, only yearly checkups are necessary and no treatment is required; preventive recommendations are warranted in those individuals with systemic disease and constitutional symptoms. Symptomatic therapy is advised in only a minority of cases. This article is meant as a guideline for physicians involved in the care of children with mastocytosis and their parents.     

Bone marrow involvement in cutaneous mastocytosis

BACKGROUND: Cutaneous mastocytosis is considered a relatively benign and indolent form of mast cell disease, which either ultimately regresses, remains stable or is only slowly progressive. Previously, it has been purported that no more than 60% of adult patients with cutaneous mastocytosis will have occult bone marrow involvement. OBJECTIVES: To investigate the frequency of bone marrow involvement in patients with mastocytosis but without systemic symptoms. METHODS: Bone marrow aspirate and trephine biopsy were performed in 13 consecutive patients with cutaneous mastocytosis attending our department. RESULTS: All but one of these patients had evidence of bone marrow involvement. Bone marrow cytogenetic abnormalities have been found in patients with cutaneous mastocytosis: all our patients who were analysed showed a normal karyotype. CONCLUSIONS: Bone marrow involvement is common in adults with cutaneous mastocytosis.     

Suplatast Tosilate for Treating Cutaneous Mastocytosis

Pediatric cutaneous mastocytosis is a rare disease caused by mast cell hyperplasia. We report the case of an infant diagnosed as cutaneous mastocytosis and seasonal allergies. The wheals, flushing, and pruritus of the mastocytosis were unresponsive to combination therapy with an antihistamine, a mast cell stabilizer (sodium cromoglycate), and a leukotriene antagonist. Addition of suplatast tosilate as a treatment for the seasonal allergy also dramatically improved his cutaneous symptoms and signs. Further trials of suplatast tosilate in selected cases of cutaneous mastocytosis are warranted.     

Diffuse Cutaneous Mastocytosis with Generalized Bullae

We report on a 9-month-old female infant with multiple tense bullae and erosions covering the entire body, including the face, scalp, and trunk. The histopathological examination revealed sub-epidermal bullae with a dense dermal cellular infiltrate. The infiltrate was identified as a collection of mast cells using toluidine blue and Giemsa stains. The direct immunofluorscence was negative. A diagnosis of cutaneous diffuse mastocytosis with generalized bullae was made based on these clinical and histopathological findings. In cases with diffuse cutaneous mastocytosis with generalized bullae, systemic involvement is more frequent and more severe compared to other types of cutaneous mastocytosis. Some lethal outcomes have been reported. This is the first reported case of diffuse cutaneous mastocytosis in the Korean literature.     

Systemic mastocytosis associated with Hodgkin’s lymphoma in a 4-year-old child

Systemic mastocytosis with associated clonal hematologic non-mast cell lineage disease (SM-AHN) represents a specific subtype of mastocytosis and is extremely rare in children. We describe a 4-year-old child with systemic mastocytosis associated with Hodgkin's lymphoma. The child had cutaneous mastocytosis and lymphadenopathy without other clinical features of SM, which was diagnosed only by bone marrow examination.     

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 in children: a clinical analysis of 71 cases

OBJECTIVE: To characterize the clinical features, response to therapy, evolution and prognosis of cutaneous mastocytosis in children. BACKGROUND: Mastocytosis in children, instead of being induced by a potentially oncogenic c-kit mutation, is probably a clonal disease with benign prognosis. METHODS: The clinicopathological features, evolution and response to treatment were analysed in 71 children with mastocytosis. RESULTS: There were 53 (75%) cases of urticaria pigmentosa, 12 (17%) cases of mastocytoma, and six (8%) cases of diffuse cutaneous mastocytosis. In 92% of cases disease onset was in the first year of life. There was a male predominance 1.8 : 1. Treatment did not modify the disease evolution. Eighty per cent of patients improved or had spontaneous resolution of the disease. CONCLUSION: The most frequent clinical form of mastocytosis was urticaria pigmentosa followed by mastocytoma and diffuse cutaneous mastocytosis. Darier's sign was present in 94% of cases. A negative Darier's sign does not rule out mastocytosis. In contrast to adults, mastocytosis in children usually has a benign course making sophisticated or invasive diagnostic tests unnecessary. A classification of paediatric cutaneous mastocytosis is proposed.     

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.     

Serum tryptase measured with B12 and G5 antibody-based immunoassays in mastocytosis patients and its relation to histamine turnover

Serum tryptase was measured with the B12 and G5 antibody-based immunoassays in 25 adult patients with mastocytosis and in 18 controls. Twelve patients had uncomplicated cutaneous mastocytosis (urticaria pigmentosa) and 13 had urticaria pigmentosa with systemic symptoms. Tryptase levels were compared with histamine turnover estimated as urinary excretion of the main histamine metabolite tele-methylimidazoleacetic acid. Elevated B12 tryptase levels (> 20 μg/L) were found in most mastocytosis patients, including five of eight patients with only cutaneous manifestations who had a low urinary histamine metabolite excretion. This indicated a higher sensitivity for diagnosing mild mastocytosis on the basis of levels of serum tryptase as opposed to urinary methylimidazoleacetic acid. However, the serum B12 tryptase assay could not differentiate between urticaria pigmentosa patients with and without systemic disease: the measurement of histamine metabolite excretion probably reflects the mast cell burden more accurately. Serum G5 tryptase levels were generally low in both controls and mastocytosis patients.     

Coexistence of two types of clinical lesions in childhood-onset mastocytosis

The vast majority of mastocytosis appear in childhood, urticaria pigmentosa (UP) and mastocytomas being the most common types. Terms such as "xanthelasmoid mastocytosis", "pseudoxanthomatous mastocytosis" or "nodular mastocytosis" have been introduced in the literature to describe the presence of yellowish papular or nodular lesions. We describe two children with cutaneous mastocytosis showing yellowish lesions in combination with other skin lesions. A 10-year-old girl presented with asymptomatic lesions in her vulva at birth, and developed brownish macules on her trunk years after. An eight-year-old boy presented with multiple yellowish papular lesions on his trunk, neck and limbs coexisting with a few clinically anetodermic lesions. No systemic involvement was found and the skin biopsy confirmed a cutaneous mastocytosis in both cases. The two patients are currently asymptomatic and are being periodically followed up. Mastocytoses may show a variety of clinical lesions, sometimes leading to misdiagnosis. Although there are previous reports, involvement of the mucosae and secondary anetoderma are not common findings in cutaneous mastocytoses. We consider that cutaneous manifestations of mastocytoses compose a clinical spectrum, thus explaining the coexistence of different clinical lesions and the development of uncommon presentations.     

Localized Mastocytosis of the Vulva

Mastocytosis is a relatively common disorder characterized by mast cell collections in the skin and other organ systems. Affected children are more likely than adults to have limited cutaneous disease. We report two patients with localized vulvar mastocytosis in the absence of other cutaneous findings and review previous reports of vulvar involvement in cutaneous mastocytosis.     

Pediatric mastocytosis.

The onset of mastocytosis occurs between birth and 2 years of age in approximately 55% of all cases; an additional 10% develop the disease before the age of 15 years. Mastocytosis in these age groups differs in many respects from mastocytosis that has its onset in adulthood. The typical presentation of pediatric-onset mastocytosis consists of cutaneous manifestations: either a solitary mastocytoma, urticaria pigmentosa, or, less commonly, diffuse cutaneous mastocytosis. Particularly in infants, bullous eruptions may occur. Mastocytosis in infants and children may involve internal organs, including the bone marrow and the gastrointestinal tract, although such manifestations appear to be less common in children than in adults. Plasma histamine levels may be elevated in pediatric-onset mastocytosis. Treatment usually involves the use of H1 and H2 antihistamines to control itching and to control the hypersecretion of gastric acid that may occur. The prognosis for children with mast cell disease is variable; approximately half of the children with urticaria pigmentosa may experience resolution of lesions and symptoms by adolescence.     

Adult Onset of Xanthelasmoid Mastocytosis: Report of a Rare Entity

Xanthelasmoid or pseudoxanthomatous mastocytosis is an extremely rare variant of diffuse cutaneous mastocytosis. Herein, we describe an adult male with cutaneous mastocytosis showing multiple widespread yellowish ovoid papules like eruptive xanthoma. A 60-year-old male visited our outpatient clinic with a 1-year history of generalized yellowish, ovoid, and skin color papular eruption located on the trunk, groin, extremities, with the modest pruritus. Vital signs were stable, and Darier''s sign was negative. No other subjective and objective signs were detected during the examination. No abnormality was detected in his diagnostic laboratory tests. Skin biopsy was taken, and histopathologic examination revealed proliferation of mast cells with ovoid and spindle nuclei with distinct cytoplasm borders around the capillaries, which was compatible with mastocytosis. Antihistamine was prescribed for pruritus control which was successful, but eruptions were persistent, and even 1-year phototherapy was not useful.     

Photochemotherapy of Dominant, Diffuse, Cutaneous Mastocytosis

Diffuse, cutaneous mastocytosis is a rare variant of cutaneous mast cell infiltration that can arise in neonates or infants as a generalized bullous eruption. The mode of transmission is suggested as autosomal dominant. We report four infants from two unrelated families with diffuse cutaneous mastocytosis whose cutaneous disease was not controlled by initial therapies. Treatment of the four infants with photochemotherapy dramatically reduced or eliminated symptoms. One course of therapy resulted in improvement, and retreatment has not been required two to six years later.     

Urticaria pigmentosa adultorum and systemic mastocytosis--diagnostic principles and therapeutic possibilities

We report on the clinical picture of urticaria pigmentosa adultorum and systemic mastocytosis. In four out of five patients, we proved systemic mastocytosis by means of a biopsy from the iliac crest, although these patients did not complain of systemic signs and symptoms. In all cases, the cutaneous changes and clinical symptoms could be improved by a four-week-heliotherapy in the North Sea summer climate; itching did not reappear but five months later. Heliotherapy is regarded as an useful alternative concerning the treatment of urticaria pigmentosa and cutaneous manifestation of systemic mastocytosis.     

Unusual cutaneous findings of urticaria pigmentosa and telangiectasia macularis eruptiva perstans associated with marked myelofibrosis

Mastocytosis is a heterogeneous group of disorders characterized by mast cell hyperplasia in the bone marrow, liver, spleen, lymph nodes, gastrointestinal tract, and skin. We present a patient with malignant mastocytosis of 11 years' duration. This case highlights the cutaneous findings of mastocytosis with systemic involvement, yet the patient maintains a relatively normal lifestyle with only minimal discomfort and only borderline normochromic anemia. Thus his course is not truly that of malignant mastocytosis but of indolent systemic mastocytosis with cutaneous findings of telangiectasia macularis eruptiva perstans (TMEP).     

Bone evaluation in ten adults with cutaneous mastocytosis

BACKGROUND: To systematically evaluate the bone status, searching for osteoporosis in patients with cutaneous mastocytosis. PATIENTS AND METHODS: In a prospective study from March 1997 to June 2000, we included all new patients examined for cutaneous signs of mastocytosis. Past history, physical examination, skin biopsy, laboratory tests, bone densitometry, cytology and histopathology of bone marrow and other complementary investigations were performed in all these patients. RESULTS: Ten patients were included. Two patients had osteoporosis. Five others had osteopenia. Four patients had bone marrow involvement due to mastocytosis. One of these four patients had myelodysplasia. DISCUSSION: This study suggests better investigation of bone density and bone marrow in patients who have cutaneous mastocytosis. Systematic histopathology of bone marrow and osteodensitometry help to detect patients with systemic involvement. Bone densitometry is particularly effective for early detection of patients at risk for fracture and is of practical interest since patients with osteoporosis can now be treated with Pamidronate.     

183例儿童皮肤型肥大细胞增生症临床及预后分析

目的 探讨儿童皮肤型肥大细胞增生症的临床特征及预后。 方法 回顾分析183例儿童皮肤型肥大细胞增生症患者的临床资料,并随访部分患者。 结果 183例患者中,色素性荨麻疹136例（74.3%）,肥大细胞瘤43例（23.5%）,弥漫性肥大细胞增生症4例（2.2%）;生后2岁内发病者179例（97.8%）。43例肥大细胞瘤患者中出生即发病者21例（48.8%）,出生后至6个月发病者17例（39.5%）,136例色素性荨麻疹患者中出生即发病者35例（25.7%）,出生至6个月发病者78例（57.3%）。伴随症状记录详细的33例患者中,10例出现伴随症状,其中9例为潮红发作。对45例患者随访3 ~ 6年（平均4年）,色素性荨麻疹患者1例于11岁时皮损完全消退,18例皮损部分消退;肥大细胞瘤患者1例皮损于8岁时完全消退,7例行皮肤活检后1年内皮损消退。口服抗组胺药可控制患者潮红、风团及水疱等症状;口服糖皮质激素可有效控制弥漫性肥大细胞增生症患儿反复发生的泛发水疱、大疱。 结论 儿童皮肤型肥大细胞增生症以色素性荨麻疹最常见,其次为肥大细胞瘤。肥大细胞瘤多于出生即发病,而色素性荨麻疹以出生后至6个月发病多见。口服抗组胺药可控制介质释放相关症状。严重的弥漫性肥大细胞增生症患者可口服糖皮质激素控制症状。