systemic mastocytosis ( sm ) is a rare , heterogeneous disorder characterized by infiltration and accumulation of mast cells ( mc ) within multiple organs , most commonly the skin . the symptoms are shared by many other and more common disorders , which may delay or hinder the diagnosis of sm . on occasion sm for that reason sm is an import differential diagnosis in patients presenting with itchy , cutaneous lesions and a history of multiple allergic reactions or diffuse systemic symptoms . a 30-year - old caucasian male with a six - to - seven - year history of small , brown cutaneous lesions on his trunk and extremities was referred for evaluation . his medical history revealed recurring itchiness and swelling of the lesions , especially after hot showers , but also from touching or rubbing on the lesions . in addition , the patient had experienced severe itchiness and flushing of the skin after an insect bite . furthermore , the patient had experienced symptoms of mild acid reflux as well as an incidence of syncope . there was no history of either shortness of breath or bone and muscle pain . objective examination of the skin revealed multiple brownish , maculopapular lesions , ranging between 0.5 - 1.0 cm in diameter on the patients trunk and extremities ( figure 1 ) . upon rubbing on the lesions , they developed erythema , swelling and the patient complained of itchiness ( positive darier s sign ) . the biopsy revealed acanthosis and intense mc infiltration of the superficial layers of the dermis , with both perivascular and diffuse infiltrates . the patient was referred to the department of dermatology , odense university hospital for further investigation and treatment . bone marrow analysis and a new skin biopsy was performed and they were both positive for kit d816v - mutation . in addition , an elevated level of alanine aminotransferase ( alat ) to 229 u / l ( normal range , 10 - 70 leucocyte , hemoglobin and thrombocyte counts were normal , as were renal function ( creatinine ) tests and blood electrolytes ( sodium and potassium ) . serum tryptase level was normal , abdominal ultrasound revealed a slightly enlarged liver , consistent with steatosis , and otherwise the examination was normal . finally , upper gastrointestinal endoscopy was performed , revealing hiatal hernia , gastroesophageal reflux disease , and 0.5 cm dark / black lesions . the patient was treated with clobetasolpropionat ( dermovat ) under occlusion and at discharge he was prescribed fexofenadin ( telfast ) 180 mg two times daily , lansoprazol 30 mg daily , and equipped with epinephrine autoinjector ( epipen 0.3 mg / dose ) in case of an anafylactic reaction . at follow - up three months later , the patient reported great improvement of the symptoms . we report of a patient with a six - to - seven - year history of diffuse maculopapular lesions , intermittent itchiness and unspecific systemic symptoms . following thorough examination , including skin biopsy with intense mc infiltration and bone marrow analysis positive for kit d816v - mutation , sm is a rare , heterogeneous disease with an estimated incidence of 1 per 150.000 per year . the disease is characterized by uninhibited proliferation of mcs in the skin and/or other tissues . mastocytosis occurs primarily in children , but there is a second peak in the incidence around age 30 - 50 years . in most cases , there are many clinical manifestations of sm and they can be attributed to both local and systemic effects of biological mediators released from mcs , as well as direct effects of infiltration of mcs in various tissues itself . the preformed mediators including histamine , heparin , eosinophil chemotactic factors of anaphylaxis , but also enzymes like tryptase , chymase , hexosaminidase among many others , are responsible for many of symptoms of sm . apart from ige , possible triggers of mc degranulation include : venoms ( insects , snakes ) , physical stimuli ( touch , rubbing , heat and cold ) , chemicals ( alcohol , nsaid , anesthetics , dextran , contrast media ) , but often the trigger for degranulation can not be identified . mcs are long - lived residents of vascularized tissues found in close proximity to blood vessels and nerves . as such they are capable of rapid delivery of their mediators into the circulation , which may subsequently result in widespread clinical symptoms . a common complaint among patients with sm is the experience of spells , in which a sudden onset of symptoms recurs in a self - limited , stereotypic fashion . these symptoms may attribute to a wide range of causes , including cardiovascular , neurologic , physiologic , pharmacologic , and other miscellaneous causes . in sm , the most common clinical presentations of systemic mastocytosis include pruritus , flushing , urticaria pigmentosa , nausea , vomiting , diarrhea , abdominal pain , headache , palpitations , dyspnea , and syncope . as in our case , the clinical course of the disease is often characterized by a history of cutaneous lesions , which are present in up to 90% of the patients with mastocytosis , thus making the skin the most commonly involved organ . urticaria pigmentosa is the most common cutaneous presentation in sm , seen in 56 - 100% of the cases . solitary mastocytoma , diffuse cutaneous mastocytosis , and teleangiectasia macularis eruotiva perstans are other presentations . a diagnosis of cutaneous mastocytosis can often be made based on the anamnesis , objective examination revealing urticaria pigmentosa , and positive darier s sign and is confirmed by a skin biopsy with an increased number of mc . the diagnosis of sm is based on the identification of neoplastic mcs as judged by using well - established morphological , and/or genetic criteria outlined by the who 2008 document . the diagnosis sm requires the presence of 1 major and 1 minor criterion or 3 minor criterions in the bone marrow or extracutaneous organs . major criterion : multifocal dense infiltrates of mcs ( > 15 mcs in aggregates ) . minor criteria : i ) mc infiltrates contain > 25% spindle - shaped cells or other atypical morphologic features ; ii ) c - kit d816v mutation ; iii ) expression of cd2 and/or cd25 on cd117 + mcs ; iv ) serum tryptase levels > 20 ng / ml ( not valid if patient has concomitant hematologic disorder ) . sm includes four major subtypes : i ) indolent sm ( the most common of sm involving mainly the skin and bone marrow ) ; ii ) sm associated with non - mast cell clonal hematological disease ( sm - ahnmd ) ; iii ) aggressive sm usually presenting without skin lesions ; and iv ) mc leukemia . irrespective of the mastocytosis category , management of mastocytosis includes avoidance of factors triggering mc degranulation and treatment of chronic and acute mast cell mediator release . patients , their caretakers and primary physicians should be informed of the elevated risk of anaphylactoid reactions . treatment of such reactions include administration of intramuscular epinephrine ( 0.3 mg ) and h1 and h2 antihistamines . oral cromolyn sodium has limited intestinal absorption , and is mostly used to help control gastrointestinal symptoms . topical steroids used under occlusion may help control pruritus and decrease the number of mcs . cytoreductive therapy is typically resolved for patients with aggressive sm and is primarily carried out in collaboration with specialists in hematology . we presented a patient with a six - to - seven year history of diffuse maculopapular lesions , intermittent itchiness and several , unspecific allergic symptoms . given the rarity of sm and the fact the many of the symptoms are shared by more common disorders , this may hinder or delay the diagnosis . when presented with a patient with chronic , itching skin lesions and a history of multiple allergic reactions to bites , drugs , anesthesia etc . sm is an important differential diagnosis , as these patients have an elevated risk of possible life threatening anaphylactoid reactions .
systemic mastocytosis ( sm ) is a rare , heterogeneous disorder characterized by infiltration and accumulation of mast cells within multiple organs , most commonly the skin . 
 given the rarity of the disease and the fact that many of its symptoms are shared by more common disorders , a diagnosis may be delayed or hindered . 
 these patients have an elevated risk of developing potentially life - threatening anaphylactoid reactions , thus underscoring the importance of keeping sm in mind as a differential diagnosis when a patient presents with chronic , itchy skin lesions and a history of multiple allergic reactions to bites , drugs , and anesthesia . 
 we present a case illustrating that features of sm common to many disorders may hinder or delay its diagnosis .