Mastocytosis is an accumulation of clonal mast cells within tissues and it is most commonly caused by an activating mutation in the KIT gene. In this study, we report a neonatal case who presented ...with diffuse cutaneous mastocytosis (CM) at birth. In China, nine other cases of neonatal-onset CM have been reported in the literature since 2006. In those cases, diffuse CM and urticaria pigmentosa were the main symptoms, and mutations in exon 17 at codon 816 in KIT were identified.
The association between Hymenoptera venom‐triggered anaphylaxis (HVA) and clonal mast cell‐related disorders (cMCD) has been known for decades. However, recent breakthroughs in peripheral blood ...screening for KIT p.D816V missense variant have revealed the true extent of this clinical association whilst adding to our understanding of the underlying aetiology. Thus, recent large studies highlighted the presence of KIT p.D816V among 18.2% and 23% of patients with severe Hymenoptera venom‐triggered anaphylaxis. A significant proportion of those patients have normal serum basal tryptase (BST) levels, with no cutaneous findings such as urticaria pigmentosa or other systemic findings such as organomegaly that would have suggested the presence of cMCD. These findings of an increased prevalence suggest that the impact of cMCD on anaphylaxis could be clinically underestimated and that the leading question for clinicians could be changed from ‘how many patients with cMCD have anaphylaxis?’ to ‘how many patients with anaphylaxis have cMCD?’. The discovery of hereditary α‐tryptasemia (HαT)—a genetic trait caused by an increased copy number of the Tryptase Alpha/Beta 1 (TPSAB1) gene‐, first described in 2016, is now known to underlie the majority of cases of elevated BST outside of cMCD and chronic kidney disease. HαT is the first common heritable genetic modifier of anaphylaxis described, and it is associated with increased risk for severe HVA (relative risk = 2.0), idiopathic anaphylaxis, and an increased prevalence of anaphylaxis in patients with cMCD, possibly due to the unique activity profile of α/β ‐tryptase heterotetramers that may potentiate immediate hypersensitivity reaction severity. Our narrative review aims to highlight recent research to have increased our understanding of cMCD and HαT, through recent lessons learned from studying their association with HVA. Additionally, we examined the studies of mast cell‐related disorders in food and drug allergy in an effort to determine whether one should also consider cMCD and/or HαT in cases of severe anaphylaxis triggered by food or drugs.
Non‐clonal mast cell disease, hereditary alpha‐tryptasemia, and anaphylaxis. Hereditary alpha‐tryptasemia (HαT) is strongly associated with clonal mast cell disease (cMCD). Either of those conditions alone is a predisposing factor for severe IgE‐dependent and IgE‐independent anaphylaxis however, the presence of HαT in patients with cMCD serves to further increase the severity of anaphylactic reactions.
Urticaria pigmentosa (UP) is a clinicopathologic term used to describe reddish-brown cutaneous macules and papules, characterized histologically by mast cell infiltration of the papillary and upper ...reticular dermis and reactive basal hyperpigmentation of the overlying epidermis. Although typically a benign, self-limited disorder of childhood, a significant proportion (up to 30%) of adolescent and adult-onset UP represents cutaneous involvement by underlying systemic mastocytosis (SM). Predicting the course of cutaneous mast cell disease has been limited by a lack of diagnostic and prognostic markers. In patients with SM, neoplastic bone marrow mast cells show aberrant surface expression of CD25. However, whether CD25 expression on cutaneous mast cells is associated with underlying SM is unknown. In this study, we performed a clinicopathologic analysis of 30 adult patients presenting with UP between 1987 and 2007. Cutaneous mast cell infiltration pattern, cytomorphology, density, and CD25 immunoreactivity were correlated with underlying or subsequent SM. On the basis of clinical and pathologic follow-up, 10 of 30 (33%) patients were diagnosed with SM and 20 of 30 (67%) with limited cutaneous mastocytosis (CM). Although cutaneous mast cell density was slightly higher in patients with SM compared to those with limited CM (P=0.047), neither mast cell cytomorphology nor infiltration pattern correlated with underlying systemic disease. However, cutaneous mast cells from all 10 patients with SM (100%) were immunoreactive for CD25, compared to only 5 of 20 (25%) with limited CM (P<0.001). Our findings suggest that immunoreactivity for CD25 in cutaneous mast cells may be useful for stratifying adult patients presenting with UP for additional clinical evaluation.
Summary
Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours arising in the gastrointestinal tract. Early detection, before metastasis occurs, is important as complete surgical excision ...achieves cure. Approximately 85% of GISTs are associated with mutations in the KIT gene, and although the majority of GISTs are sporadic, familial GISTs have been identified. Several families with multiple GIST tumours have also been described with various cutaneous findings including hyperpigmentation, multiple lentigines, vitiligo and urticaria pigmentosa. We discuss a 6‐year‐old boy who presented with an unusual pattern of hyperpigmentation in association with a family history of GIST. A causative KIT mutation was identified in DNA from the pigmented skin and from the resected GIST, and the patient was referred to the Paediatric Gastroenterology department for GIST screening. The term ‘GIST cutaneous hyperpigmentation disease’ has been suggested previously for the association of familial GIST with cutaneous hyperpigmentation caused by a germline KIT mutation.
Cutaneous mastocytosis is defined by the presence of mast cells within the skin in the absence of other criteria for the diagnosis of systemic mastocytosis. Mast cells are characterized by an ...abundant granular cytoplasm and a round to oval or spindle-shaped nuclei. The presence of mast cells with bilobed and multilobed nuclei in cutaneous mastocytosis is a rare phenomenon and has been rarely reported in the literature. To our knowledge, there are only 4 reported cases of cutaneous mastocytosis with atypical mast cells. We hereby report a case of urticaria pigmentosa in a 7-year-old female patient. The patient presented with asymptomatic skin lesions of several years duration over the neck and left scapular area. Histopathological examination revealed the presence of middermal perivascular infiltrates mainly composed of mast cells, few lymphocytes, and eosinophils. Most mast cells showed pleomorphic nuclei with bilobed and multilobed morphology that revealed a positive expression for CD117, tryptase, CD68, and Giemsa stains. Based on these findings the diagnosis of urticaria pigmentosa with atypical mast cells was made. Additional tests to rule out systemic involvement were performed. All values, including a tryptase level, were within normal limits. No changes were noted after 1-year follow-up.
ABSTRACT
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.
Since beginning omalizumab, she has continued with 50 mg of doxepin daily and 150 mg of ranitidine twice daily. Omalizumab is unlikely to affect mast cell turnover but has been shown to decrease ...serum free IgE levels,2 downregulate FcεRI on mast cells,3 and increase the threshold above which mast cell activation is triggered.
Urticaria pigmentosa is a rare disorder characterized by an abnormal systemic proliferation of mast cells. In this condition, various triggers can induce either cutaneous histamine release, resulting ...in rash, or generalized histamine release, resulting in symptomatic hypotension, syncope, or in its severest form, an anaphylactoid reaction resistant to most resuscitative measures. Many anesthetic agents and adjuncts are known potential triggers, and patients who require surgery or procedures under anesthesia must be managed carefully. In this review, we describe the safe use of general anesthesia for electroconvulsive therapy in a patient with urticaria pigmentosa and discuss the association between psychiatric disorders and mastocytoses.
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