Diffuse cutaneous mastocytosis with bullous lesions and pulmonary involvement: a rare case.

Mastocytosis is defined as a heterogeneous group of disorders characterized by an accumulation of mast cells in one or more organs, particularly in the skin, bone marrow, liver, spleen and lymph nodes. However here we describe an 11-month-old girl child presented with diffuse cutaneous mastocytosis with bullous lesion, having pulmonary involvement, which is very rare and there is no available case report from India.

What was known?

Mastocytosis is an accumulation of mast cells in one or more organs, commonly in the skin, bone marrow, liver, spleen and lymph nodes.

Introduction

Mastocytosis is a rare disease, defined as a disorderly infiltration with mast cells in several tissues.[12] The prevalence of the disease is approximately one in 25-30,000 and its clinical manifestations vary with age of onset (pediatric vs. adult), disease variant (systemic vs. cutaneous), severity (indolent vs. aggressive) and associated hematologic disorders.[3]

Case Report

A 4-month-old female infant presented with generalized blisters that were first noted when she was 3-months-old. The lesions were first observed on the hands and feet and spread to the scalp, face and trunk. The parents also complained that the child was having recurrent episodes of bouts of cough, with respiratory distress along with increased body temperature and the child becomes restless and the whole body becomes red during these attacks. However these improve spontaneously in few hours and increases on child handling. No family history of any skin diseases or atopy.

Physical examination revealed multiple, tense vesicles, bullae, erosions and hemorrhagic crusted lesions over the face, scalp and trunk [Figure 1a and b]. The Darier's sign was present on the thigh. There was no evidence of organomegaly or lymphadenopathy. A complete blood cell count and the biochemical profiles were within the normal limits. Serum tryptase was more than 200 IU. Chest X-ray was done for repeated episodes of respiratory distress, which shows reticulogranular patterns on both lung fields, but we were unable to find out any infectious cause for such infiltration.

Figure 1

(a) Multiple tense bullae and erosions developed with peau dæorange-like skin on the face, scalp, and trunk, (b) Bilateral pulmonary infiltration in chest X-ray

The histological examination of a biopsy taken from the thigh revealed sub-epidermal bullae with a dense infiltration of mast cells and in the upper dermis [Figure 2]. The toluidine blue and Giemsa stains showed that almost all of the infiltrating cells in the dermis were mast cells [Figure 3]. The direct immunofluorescence was negative. The diagnosis of dilated cardiomyopathy (DCM) was made based on these clinical and histopathological findings. The patient was treated with oral betamethasone and oral hydroxyzine. On follow-up after 1 month, the skin lesions were improved, pulmonary infiltration were regressed and there was no such sudden attacks of the bouts of coughs or respiratory distress after starting steroid and antihistaminic.

Figure 2

(a) Sub-epidermal bullae with a dense cellular infiltration in the upper dermis (H and E, ×200). (b) Dense mast cell infiltration with some eosinophils in the upper dermis (H and E, ×400)

Figure 3

Mast cells were stained with toluidine blue

Discussion

Pulmonary infiltration is rare in cutaneous mastocytosis. Patients usually presented with sudden onset tachypnoea, tachycardia, respiratory distress, anorexia, restlessness, irritability with sudden onset high fever and the whole body becomes flushed. These symptoms may precipitate due to any cause that stimulates the release of vasodialtory cytocines from the mast cell masses in the skin or lungs. Pulmonary infiltrations usually resolved in parallel with cutaneous lesions and usually do not require special treatment if the child does not present with repeated anaphylaxis. Approximately 65% of individuals with mastocytosis present with disease in childhood; nearly 55% of these patients have manifestations of disease by the age of 2 years. The remaining 35% of those that develop their disease after puberty are classified as adult onset. Although the occurrence of mastocytosis appears to be sporadic, there are reports of familial mastocytosis with dominance in several families. 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. Radiographic evidence of lung involvement in DCM occurs in 16-20% of cases. The changes observed are reticulo-nodular opacities, nodules and cysts. For a diagnosis of mastocytosis, at least one major and one minor, or at least 3 min or criteria should be met. Major criteria includes the presence of multifocal dense infiltrates of mast cells in bone marrow or other extracutaneous organ(s) (>15 mast cells in aggregate) and minor criterias are: (1) Mast cells in bone marrow or other extracutaneous organ(s) show an abnormal morphology (>25%). (2) C-kit mutation at codon 816 in extracutaneous organ(s). (3) Mast cells in bone marrow express CD2 and/or CD25. (4) Serum total tryptase >20 ng/mL. Stains such as toluidine blue or Giemsa, and the demonstration of mast cell tryptase by immunohistochemistry have been used to identify mast cells within cutaneous tissues. A total tryptase >20 ng/ml in association with a total tryptase to β tryptase ratio of >20 identifies patients more likely to have systemic mastocytosis.[4] Testing for C-kit D816V mutation has both diagnostic and prognostic implications. >80% of cases of systemic mastocytosis show the presence of the C-kit D816V activating mutation. It represents a potential drug target. The allele-specific assay to detect the D816V mutation in deoxyribonucleic acid (DNA) from archived formalin-fixed paraffin-embedded tissues has been found to be more sensitive than the traditional DNA sequencing techniques. These mutations confer resistance to imatinib and those patients positive for D816V, are in general fully or partially resistant to tyrosine kinase inhibitors. The extent of the skin abnormality can be evaluated by the SCORMA score. From a theoretical point of view combined H1 and H2-blockers may be useful because these drugs have been reported to reduce unprovoked attacks.[56] Anti immunoglobulin E (IgE) (omalizumab) has been shown to reduce attacks in mastocytosis patients.[7] Pre-treatment with anti-IgE probably will only be effective after several weeks of treatment and only in situations where IgE-mediate processes occur. Imatinib inhibits wild type kit (wtkit) and suppresses proliferation of the human mast cell (HMC)- 1V560G cell line. It has been shown to have a therapeutic role in both systemic and cutaneous mastocytosis carrying C-kit mutation, while it is ineffective on inhibiting the growth of HMC-1V560G, D816V cells. Apart from wtkit, kit molecules carrying mutations in the extracellular, transmembrane and juxtamembrane domains, such as V560G, F522C and K509I, remain sensitive to imatinib. In summary, pediatric onset mastocytosis is an unusual disease with an often benign course. The disease in children is less likely to have a systemic component. Review of the literature suggests that those at potential risk for experiencing shock or sudden death include children with extensive bullous cutaneous involvement, those with symptoms of vasodilatation, flushing and hypotension and those with early onset of disease.

What is new?

Pulmonary infiltration with mast cells in cutaneous mastocytosis can present with sudden onset respiratory distress.