Diffuse Cutaneous Mastocytosis: A Current Understanding of a Rare Disease.

Mastocytosis is a heterogeneous disease characterized by the expansion and accumulation of neoplastic mast cells in various tissues. Diffuse cutaneous mastocytosis (DCM) is a rare and most severe form of cutaneous mastocytosis, which typically occurs in childhood. There have been reports of a familial DCM with specific gene mutations, indicating both sporadic and hereditary factors involved in its pathogenesis. DCM is associated with severe MC mediator-related symptoms and an increased risk of anaphylaxis. The diagnosis is based on the appearance of skin lesions, which typically show generalized thickening, erythroderma, blistering dermographism, and a positive Darier's sign. Recognition, particularly in infants, is challenging due to DCMs resemblance to other bullous skin disorders. Therefore, in unclear cases, a skin biopsy is crucial. Treatment focuses on symptom management, mainly including antihistamines and mast cell stabilizers. In extremely severe cases, systemic steroids, tyrosine kinase inhibitors, phototherapy, or omalizumab may be considered. Patients should be equipped with an adrenaline autoinjector. Herein, we conducted a comprehensive review of literature data on DCM since 1962, which could help to better understand both the management and prognosis of DCM, which depends on the severity of skin lesions, intensity of mediator-related symptoms, presence of anaphylaxis, and treatment response.

Molecular defects in mastocytosis: KIT and beyond KIT.

In all variants of mastocytosis, activating KIT mutations are frequently found. In adults, neoplastic mast cells (MCs) cells show the KIT mutation D816V, whereas in children, MCs invading the skin are frequently positive for non-KIT D816V mutations. The clinical course and prognosis of the disease vary among patients with systemic mastocytosis (SM). Additional KIT-independent molecular defects might cause progression. Additional oncogenic lesions have recently been identified in advanced SM. In advanced SM the presence of additional genetic lesions or altered signaling worsening the prognosis might lead to the use of alternative therapies such as combined antisignaling targeted treatments or stem cell transplantation.

Treatment of cutaneous mastocytosis.

Therapy of cutaneous mastocytosis is directed towards skin and systemic symptoms due to mediator release and targeted on skin lesions. Symptomatic therapy of cutaneous mastocytosis involves agents that inhibit the release of mediators or antagonize H1 and H2 receptors such as antihistamines ketodifen and Aspirin. Disodium cromoglycate has no effect of the cutaneous symptoms of cutaneous mastocytosis. Skin-targeted therapies that lead to a resolution of the lesions of cutaneous mastocytosis are psoralen-photochemotherapy and topical corticosteroid therapy either by occlusion or intralesional injection for a limited number of lesions. There is no treatment that permanently cures cutaneous mastocytosis and patient selection will therefore have to be made on the basis of the clinical manifestations, onset of disease, the probability of spontaneous involution and the severity of cutaneous and systemic symptoms.

Cutaneous mastocytosis in adults. evaluation of 14 patients with respect to systemic disease manifestations.

BACKGROUND AND OBJECTIVE: Systemic mastocytosis is a rather rare disorder involving the skin and several other organs. The aim of this study was to analyse the extent of extracutaneous manifestations in 14 adult patients who presented with prominent cutaneous involvement within the last 5 years. RESULTS: The cutaneous lesions were clinically diagnosed as telangiectasia macularis eruptiva perstans in 2 patients, urticaria pigmentosa of varying extent in 11 and diffuse erythrodermic mastocytosis in 1 patient. All patients had extracutaneous manifestations with involvement of one additional organ system in 6/14 cases, two in 5/14 and three in 3/14. Ten out of 14 patients suffered from generalized pruritus, and 11/14 reported mild wheal formation, while 3/14 with multi-organ involvement mentioned recurrent flushing episodes. The gastro-intestinal tract was involved in 8/14 cases with an increase in gastric and colon mucosal mast cells in 5/8 cases and gastroduodenitis in 2. Bone marrow involvement was seen in 7/13 patients, hepatosplenomegaly in 2, anaemia in 2 and thrombocytopenia in 3. The disease had a duration of 0.5-32 years, clinical symptoms remaining basically unchanged. Malignant transformation was not seen; only 1 patient developed myelodysplastic syndrome within 2 years after the first cutaneous lesions. CONCLUSIONS: Our study shows that extracutaneous involvement should be carefully considered in adult patients with cutaneous mastocytosis. Systemic multi-organ mast cell disease in adults is a long-lasting disorder with recurrent episodes of varying clinical symptomatology. However, the disease shows rather slow progression, and malignant transformation is rare. Satisfactory management is achieved by symptomatic oral drug intake.

Short- and long-term effectiveness of oral and bath PUVA therapy in urticaria pigmentosa and systemic mastocytosis.

BACKGROUND: Previous studies have shown that oral PUVA is effective in urticaria pigmentosa. Long-term results, however, are unknown. OBJECTIVE: We studied the long-term effectiveness of oral PUVA treatment in urticaria pigmentosa as well as in systemic mastocytosis. In addition, the success of bath PUVA was examined in these diseases. METHODS: Twenty patients with urticaria pigmentosa and systemic mastocytosis treated by oral PUVA were examined retrospectively for a time period of up to 18 years. We studied the duration of improvement and correlated these results with the total PUVA dose, the skin type and the age of onset. Four patients were treated by bath PUVA therapy. RESULTS: In oral PUVA therapy an improvement was seen in 14 out of 20 patients (70%). There was no difference in the response rate between urticaria pigmentosa and systemic mastocytosis and there was no correlation with the total PUVA dosage. The duration of the treatment's success ranged from a few weeks to more than 10 years. 25% of the patients showed an improvement for more than 5 years. Patients with onset during childhood and early adolescence and patients with skin types I and II responded favourably to the treatment. Bath PUVA therapy was without effect in our 4 patients. CONCLUSION: Oral PUVA is very effective for the long-term treatment of urticaria pigmentosa as well as systemic mastocytosis.