Pediatric Bullous Mastocytosis: Diagnostic Challenges and Therapeutic Strategies

Pediatric Bullous Mastocytosis: Diagnostic Challenges and Therapeutic Strategies | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Pediatric Bullous Mastocytosis: Diagnostic Challenges and Therapeutic Strategies mahmoud ladhar, olfa fendri, manel hsairi, imene moalla, kmar turki, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8678247/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background Mastocytosis is a rare disorder characterized by abnormal proliferation and accumulation of mast cells. In children, it is most often limited to the skin. Diffuse cutaneous mastocytosis is the rarest form and typically presents during infancy, frequently with extensive bullous lesions. Due to its rarity and clinical resemblance to other bullous dermatoses, early diagnosis remains challenging. Case presentation We report the case of a 9-month-old female infant admitted for an extensive pruritic bullous and ecchymotic eruption involving the thorax, limbs, and scalp. Physical examination revealed thickened infiltrated skin and a positive Darier’s sign, while mucous membranes were spared. Routine laboratory investigations were normal. Skin biopsy showed a dense subepidermal dermal infiltrate composed predominantly of mast cells arranged in confluent sheets. Immunohistochemical staining demonstrated strong and diffuse CD117 positivity. Serum tryptase levels were elevated, supporting the diagnosis of diffuse cutaneous mastocytosis. The patient was treated with topical corticosteroids, sterile dressings, and oral antihistamines, with complete resolution of skin lesions and no systemic complications. Conclusion Diffuse cutaneous mastocytosis should be considered in infants presenting with bullous skin lesions. Histological and immunohistochemical confirmation is essential for diagnosis. Although prognosis is generally favorable, careful follow-up is required due to the risk of severe mediator-related manifestations. Clinical trial number: not applicable Diffuse cutaneous mastocytosis bullous dermatosis serum tryptase Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Mastocytosis encompasses a group of rare disorders characterized by abnormal proliferation of mast cells in one or more organs. Clinical expression is highly variable and depends both on mast‑cell mediator release and tissue infiltration. Gain‑of‑function somatic mutations of the KIT gene are identified in more than 80% of pediatric mastocytosis cases ( 1 ). In children, cutaneous involvement is the most common manifestation. According to the WHO classification, cutaneous mastocytosis is divided into three clinical forms ( 2 ). Urticaria pigmentosa is the most frequent form, accounting for approximately 65% of cases ( 3 ), while solitary mastocytoma is observed in 9–35% ( 3 , 4 ). Diffuse forms, such as bullous mastocytosis, are much rarer but may lead to more severe symptoms. This clinical diversity may complicate diagnosis and highlights the importance of reporting rare or atypical cases. The present case illustrates a particular manifestation of this disease, providing further insight into its clinical variability. Case Report We report the case of a 9‑month‑old female infant from Sfax with no significant past medical history, admitted to the pediatric intensive care unit for management of extensive oozing epidermal detachment. Symptoms began five days prior to admission with a flu‑like syndrome, followed by the appearance of an erythematous rash involving the thorax, trunk, and all four limbs, which rapidly progressed to bullous detachment within 24 hours ( Fig. 1 ) . A history of symptomatic treatment with paracetamol and homeopathic remedies was reported. Due to the severity and extent of skin lesions associated with respiratory deterioration, the patient was admitted to the intensive care unit. She was febrile, tachypneic with hoarseness, and hemodynamically stable. Dermatological examination revealed areas of epidermal detachment with a ‘wet sheet’ appearance; Darier’s sign was positive in the axillary folds, neck folds, and back. The background skin was ecchymotic with hemorrhagic bullae overlying ecchymotic areas, particularly on the neck ( Fig. 2 – 3 ). There was no mucosal or diaper area involvement. The scalp was also affected ( Fig. 4 ). Initial laboratory investigations showed an inflammatory response with CRP of 45 mg/L, leukocyte count of 9,930/mm³, and eosinophils at 20%. Upon admission, the patient was intubated and mechanically ventilated due to respiratory distress. Skin care included sterile wet dressings, paraffin gauze, and petroleum jelly, along with systemic dexamethasone. Toxic epidermal necrolysis and staphylococcal scalded skin syndrome were initially suspected, prompting treatment with intravenous immunoglobulins for two days and antibiotics (teicoplanin combined with amoxicillin–clavulanic acid). Skin swab cultures revealed various staphylococcal species. On day two of hospitalization, bullous mastocytosis was suspected based on the infiltrated yellowish plaques on the flank, glottic edema, and respiratory distress. Serum tryptase level was markedly elevated at 73.7 µg/L (normal < 8.4 µg/L). The diagnosis of diffuse cutaneous mastocytosis was confirmed by skin biopsy showing a thin epidermis with parakeratotic scales and intra‑ and subepidermal micro‑abscesses. The underlying dermis contained a dense band‑like inflammatory infiltrate composed predominantly of confluent sheets of mast cells, with scattered eosinophils and neutrophils. Immunohistochemistry demonstrated intense and diffuse CD117 staining. The patient was treated with topical hydrocortisone, antiseptic cream, and oral antihistamines. The hospital course was complicated by suspected care‑related infection requiring clindamycin, and by right internal jugular vein thrombosis. Skin condition improved within days of treatment, with re‑epithelialization, reduced erythema, and absence of new bullae ( Fig. 5 ). The patient was discharged home after 20 days of hospitalization, including 11 days in intensive care and 7 days of mechanical ventilation. Parents received education on trigger avoidance and follow‑up care. At 7‑month follow‑up, complete resolution of lesions was observed ( Fig. 6 ). Discussion The prevalence of pediatric mastocytosis is estimated at 1 to 10 cases per 100,000 individuals ( 5 , 6 ). Between 60% and 80% of patients develop skin lesions during the first year of life ( 7 ). In children, most cases are benign, and the cutaneous form is the most frequent. Based on the clinical appearance of skin involvement, cutaneous mastocytosis (CM) is divided into three main forms: maculopapular cutaneous mastocytosis (MPCM), also known as urticaria pigmentosa; diffuse cutaneous mastocytosis (DCM); and cutaneous mastocytoma ( 8 ). MPCM is the most common form and presents as red-brown macules or slightly elevated papules measuring 0.5 to 1 cm, predominantly involving the trunk and extremities, while the face, scalp, palms, and soles are generally spared ( 9 ). Mastocytoma is characterized by a nodular or plaque-like lesion, solitary or up to a maximum of three lesions. DCM is a rare and severe form, and its bullous variant is an extremely rare entity, with an estimated occurrence of 1 per 1,000,000 individuals ( 10 ). It usually presents at birth (congenital or infantile form) or during early childhood ( 5 ). Clinically, it manifests as erythroderma and pachydermia, with thickened, leathery skin showing an “orange peel” appearance due to mast cell infiltration, associated with bullae and blisters ( 11 ). A positive Darier’s sign is pathognomonic for all forms of CM ( 7 , 11 ). Pruritus is frequently present ( 12 ), and hyperpigmentation may persist into adulthood. Other systemic symptoms, such as flushing and gastrointestinal disturbances, may occur as a result of histamine and other mast cell mediator release into the bloodstream ( 6 , 13 ). In our case, toxic epidermal necrolysis (Lyell syndrome) or a staphylococcal skin infection was initially suspected before the diagnosis of bullous mastocytosis was established. Indeed, the clinical presentation may resemble Stevens–Johnson syndrome/toxic epidermal necrolysis or other pediatric bullous disorders, including staphylococcal scalded skin syndrome, linear IgA bullous dermatosis, epidermolysis bullosa, bullous impetigo, and bullous erythema multiforme ( 5 , 6 ). The clinical manifestations of bullous diseases in children are often very similar, making clinical diagnosis challenging. Roux et al. ( 6 ) reported a similar case that was initially diagnosed and treated as Stevens–Johnson syndrome, with the diagnosis of bullous mastocytosis subsequently confirmed by skin biopsy. The vast majority of mastocytosis cases result from a somatic mutation of the proto-oncogene c-KIT ( 7 ), which encodes the KIT receptor, also known as CD117, a tyrosine kinase receptor responsible for mast cell differentiation, maturation, and proliferation ( 5 , 7 ). Mutations in c-KIT lead to constitutive activation of the KIT receptor, resulting in mast cell proliferation within tissues ( 5 , 7 , 13 ). Sotlar et al. reported c-KIT gene mutations in skin biopsies from 16 of 37 pediatric patients (43%) with cutaneous involvement ( 14 ). The diagnosis of cutaneous mastocytosis is often challenging and relies on a combination of clinical and biochemical findings ( 5 , 7 ). Initial evaluation includes a complete clinical and dermatological examination, complete blood count, blood biochemical tests, and serum tryptase measurement, as well as skin biopsy with histological examination. Tryptase is a serine protease primarily synthesized and stored in mast cells ( 15 ). Baseline serum tryptase levels reflect the total mast cell burden of the body, making it useful for the diagnostic workup and follow-up of systemic mastocytosis. A baseline serum tryptase level greater than 20 ng/mL is defined by the WHO as a minor diagnostic criterion for systemic mastocytosis ( 11 ), particularly when associated with cytopenias and organomegaly ( 6 , 16 ). However, elevated tryptase levels may strongly suggest the diagnosis without definitively confirming it. Several other conditions are associated with elevated baseline serum tryptase levels, including hereditary alpha-tryptasemia, allergic diseases, chronic eosinophilic leukemia, and certain nephropathies ( 17 ). In our case, serum tryptase levels were elevated in the absence of other signs of systemic involvement. Elevated serum tryptase levels are commonly observed in patients with extensive skin involvement, particularly those with diffuse cutaneous mastocytosis ( 11 ). The diagnostic gold standard relies on formalin-fixed skin biopsy with CD117 immunostaining, demonstrating significant dermal infiltration by mast cells ( 5 , 7 , 13 ). The major histological criterion for diagnosis, with a specificity ≥ 95%, is a mast cell density greater than 139 mast cells/mm² in the superficial dermis ( 18 ). However, skin biopsy is not systematically required and is mainly indicated in doubtful cases, when Darier’s sign is not evident or when skin lesions are atypical ( 18 , 19 ). Genetic analysis for activating KIT mutations in skin and peripheral blood is particularly important in uncertain cases, as it represents the most specific criterion for cutaneous mastocytosis lesions. Determination of KIT D816V mutational status using highly sensitive quantitative real-time PCR is recommended ( 18 ). To date, no curative pharmacological treatment exists for mastocytosis ( 5 ). The main goal of cutaneous mastocytosis management is to reduce and control mast cell mediator release ( 5 , 7 , 10 , 13 ). The first and most important preventive measure is avoidance of triggering factors. Numerous environmental and pharmacological factors may induce mediator release, including extreme temperatures (heat and cold), fever, infections, stress, physical exercise, skin friction, nonsteroidal anti-inflammatory drugs, opioids, contrast agents, dextromethorphan, and certain antibiotics such as quinolones ( 7 , 13 ). This highlights the importance of parental education prior to discharge and during follow-up visits. In our case, paracetamol was not considered a risk medication, but a preceding infection may have acted as the triggering factor. The use of an epinephrine auto-injector in cases of severe hypotension or shock is recommended, particularly in children with extensive skin involvement, a history of severe systemic symptoms or anaphylaxis, and markedly elevated serum tryptase levels. Symptomatic treatment of diffuse cutaneous mastocytosis can be achieved under sterile conditions through the application of topical therapies and oral medications, such as topical corticosteroids or topical sodium cromoglycate, and oral antihistamines ( 7 , 13 ). The use of systemic corticosteroids is limited by their numerous side effects but may be indicated for short durations in cases of extensive lesions and recurrent bullae ( 6 , 8 ). Refractory cases may be treated with omalizumab (an anti-IgE monoclonal antibody) or psoralen plus ultraviolet A photochemotherapy ( 7 , 8 ). Follow-up is recommended every 6 to 12 months. Parents should be informed of the rare possibility of progression to systemic disease ( 7 ). A recent literature review showed that approximately 1 in 100 children with cutaneous mastocytosis may develop a systemic form ( 20 ). During follow-up, our patient experienced an episode of wheezing dyspnea. Disease evolution may be characterized by complete absence of symptoms or, conversely, by the occurrence of mediator-related symptoms such as pruritus, flushing, bullae, wheezing, abdominal pain, diarrhea, hypotension, headaches, and depression ( 8 ). In general, most pediatric patients with cutaneous mastocytosis experience spontaneous regression around puberty and have a favorable prognosis ( 5 , 18 , 21 ), despite a reported mortality rate of up to 24%, mainly due to anaphylactic shock and gastrointestinal hemorrhage ( 8 ). A recent prospective study evaluating the long-term outcome of pediatric mastocytosis in 28 children reported diffuse bullous involvement in 6% of cases, with a favorable outcome observed in 25% of those patients ( 22 ). Conclusion Pediatric bullous mastocytosis is a rare and underdiagnosed condition. Early recognition relies on careful correlation of clinical, histopathological, and biological findings. Identification of Darier’s sign, CD117‑positive mast‑cell infiltration, and elevated serum tryptase are essential for diagnosis. Symptomatic management is usually effective, but vigilant monitoring remains necessary given the potential for severe systemic manifestations. Declarations Ethics approval and consent to participate The study was conducted in accordance with ethical standards, and ethical principles were fully respected. Consent for publication Informed written consent was obtained from the parents of the patients for publication of the paper and all informations within it. The proof of consent can be requested at any time Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding The authors received no specific funding for this work. Authors' contributions All authors contributed to the study conception, data collection, analysis, and manuscript preparation. All authors read and approved the final manuscript. Acknowledgements The authors would like to thank all participants and collaborators who contributed to this study. References Polivka L, Bodemer C. Mastocytose pédiatrique. Horizons Hémato. 2018. Valent P, Akin C, Metcalfe DD. Mastocytosis: 2016 updated WHO classification and novelemergingtreatment concepts. Blood 16 mars. 2017;129(11):1420–7. Ben-Amitai D, Metzker A, Cohen HA. Pediatriccutaneousmastocytosis:areview of 180 patients. Isr Med Assoc J IMAJ mai. 2005;7(5):320–2. Popadic S, Lalosevic J, Lekic B, Gajić-Veljic M, Bonaci-Nikolic B, Nikolic M. Mastocytosis in children:a single-center long-term follow-up study. Int J Dermatol mai. 2023;62(5):616–20. Lange M, Hartmann K, Carter MC, Siebenhaar F, Alvarez-Twose I, Torrado I, et al. Molecular Background, ClinicalFeatures and Management of PediatricMastocytosis:Status 2021. Int J Mol Sci 4 mars. 2021;22(5):2586. Roux J, Pham CT, Yale K, Rojek NW, Linden K, Doan L. A rare case of pediatriccutaneousbullousmastocytosis. JAAD Case Rep. 25 déc2024;57:14–7. Castells M, Metcalfe DD, Escribano L. Diagnosis and treatment of cutaneousmastocytosis in children:practicalrecommendations. Am J Clin Dermatol 1 août. 2011;12(4):259–70. Giona F, PediatricMastocytosis. An Update. Mediterr J Hematol Infect Dis 1 nov. 2021;13(1):e2021069. Ridlo M, Mahadi IDR, Siregar R. Single Case Report: Diffuse CutaneousMastocytosiswithGeneralizedBullaeMimickingBullousPemphigoid. In:Proceedings of the 2nd International Conference on Tropical Medicine and InfectiousDisease (ICTROMI). 2019; 1:436–440. Asati DP, Tiwari A. Bullousmastocytosis in a 3-month-old infant. IndianDermatol Online J. 2014;5(4):497–500. Ługowska-Umer H, Czarny J, Rydz A, Nowicki RJ, Lange M. Current Challenges in the Diagnosis of PediatricCutaneousMastocytosis. Diagnostics. 1 déc2023;13(23):3583. Deverrière G, Carré D, Nae I, Cailliez D, Boulloche J. Mastocytose bulleuse diffuse du nourrisson: une forme clinique rare. Arch Pédiatrie. 1 juill2012;19(7):722–5. Almheiri SK, Pakran J, AlFalasi AA, El Bahtimi R. BullousMastocytosis: A Rare Variant of Diffuse CutaneousMastocytosis. Cureus. 16(1):e51660. Sotlar K, Escribano L, Landt O, Möhrle S, Herrero S, Torrelo A, et al. One-step detection of c-kit point mutations using peptide nucleicacid-mediatedpolymerasechainreactionclamping and hybridization probes. Am J Pathol mars. 2003;162(3):737–46. Valent P, Hoermann G, Bonadonna P, Hartmann K, Sperr WR, Broesby-Olsen S, et al. The Normal Range of Baseline Tryptase Should Be 1 to 15 ng/mL and CoversHealthyIndividualsWith HαT. J Allergy Clin ImmunolPract oct. 2023;11(10):3010–20. Carter MC, Metcalfe DD, Komarow HD, Mastocytosis. ImmunolAllergy Clin North Am févr. 2014;34(1). 10.1016/j.iac.2013.09.001 . Rydz A, Lange M, Ługowska-Umer H, Sikorska M, Nowicki RJ, Morales-Cabeza C, et al. Diffuse CutaneousMastocytosis: A CurrentUnderstanding of a Rare Disease. Int J Mol Sci 23 janv. 2024;25(3):1401. Ługowska-Umer H, Czarny J, Rydz A, Nowicki RJ, Lange M. Current Challenges in the Diagnosis of PediatricCutaneousMastocytosis. Diagnostics. 1 déc2023;13(23):3583. Gebhard J, Horny HP, Kristensen T, Broesby-Olsen S, Zink A, Biedermann T, et al. Validation of dermatopathologicalcriteria to diagnose cutaneouslesions of mastocytosis: importance of KIT D816V mutation analysis. J EurAcadDermatolVenereol JEADV août. 2022;36(8):1367–75. Lange M, Niedoszytko M, Nedoszytko B, Łata J, Trzeciak M, Biernat W. Diffuse cutaneousmastocytosis:analysis of 10 cases and a brief review of the literature. J EurAcadDermatolVenereol JEADV déc. 2012;26(12):1565–71. Hartmann K, Escribano L, Grattan C, Brockow K, Carter MC, Alvarez-Twose I, et al. Cutaneous manifestations in patients withmastocytosis: Consensus report of the EuropeanCompetence Network on Mastocytosis; the American Academy of Allergy, Asthma&Immunology and the EuropeanAcademy of Allergology and ClinicalImmunology. J Allergy Clin Immunol janv. 2016;137(1):35–45. Popadic S, Lalosevic J, Lekic B, Gajić-Veljic M, Bonaci-Nikolic B, Nikolic M. Mastocytosis in children:a single-center long-term follow-up study. Int J Dermatol. 2023;62(5):616–20. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 14 Mar, 2026 Reviewers agreed at journal 01 Mar, 2026 Reviewers invited by journal 24 Feb, 2026 Editor invited by journal 30 Jan, 2026 Editor assigned by journal 29 Jan, 2026 Submission checks completed at journal 29 Jan, 2026 First submitted to journal 23 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8678247","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":596139398,"identity":"7e482826-ce34-409d-82bf-cc706121ae80","order_by":0,"name":"mahmoud ladhar","email":"","orcid":"","institution":"Hopital Universitaire Hedi Chaker","correspondingAuthor":false,"prefix":"","firstName":"mahmoud","middleName":"","lastName":"ladhar","suffix":""},{"id":596139400,"identity":"1913ec54-76ff-43f5-a7ce-58a936ed195d","order_by":1,"name":"olfa fendri","email":"","orcid":"","institution":"Hopital Universitaire Hedi 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diameter, located on the trunk, yellowish-brown in color\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8678247/v1/38ee819042aca3e203f801f6.png"},{"id":103583772,"identity":"fd27daf1-de2b-45c0-859d-48fe8a9e2df8","added_by":"auto","created_at":"2026-02-27 10:44:48","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":400532,"visible":true,"origin":"","legend":"\u003cp\u003eAppearance upon admission to intensive care showing areas of epidermal detachment \u0026nbsp;overlying an ecchymotic areas\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8678247/v1/13681416800a86a095336e94.png"},{"id":103583777,"identity":"3acf29fb-204e-456e-9dbb-f785a4b18638","added_by":"auto","created_at":"2026-02-27 10:44:49","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":443525,"visible":true,"origin":"","legend":"\u003cp\u003eWet line appearance resting on a bruised base\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8678247/v1/57d4bd4d83784c55791152a8.png"},{"id":103583776,"identity":"8e5f3504-7ee7-45d0-a992-11134e45df1f","added_by":"auto","created_at":"2026-02-27 10:44:49","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":297241,"visible":true,"origin":"","legend":"\u003cp\u003eErythematous-necrotic appearance with blisters on the scalp\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8678247/v1/68e3e7f9c9082bfd0b730c4f.png"},{"id":104399004,"identity":"f51963b2-c3b2-42d2-873f-89f181f4d036","added_by":"auto","created_at":"2026-03-11 12:04:28","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":240150,"visible":true,"origin":"","legend":"\u003cp\u003eAbsence of new blisters or vesicles with hyperemic scars\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-8678247/v1/6da9676b2173e3adf973a72b.png"},{"id":103583774,"identity":"ea1e6179-f897-4cb4-8ac2-1c0e1b9f3a86","added_by":"auto","created_at":"2026-02-27 10:44:48","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":132594,"visible":true,"origin":"","legend":"\u003cp\u003eThe erosions are healing and the post-inflammatory hypopigmentation is minimal.\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-8678247/v1/e66ad9945708dcd475352e8b.png"},{"id":104407461,"identity":"d92d1ee0-526f-4927-bcb4-25be5058228b","added_by":"auto","created_at":"2026-03-11 12:38:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2728287,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8678247/v1/a141d23d-c926-48fe-a95c-597cb701052a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Pediatric Bullous Mastocytosis: Diagnostic Challenges and Therapeutic Strategies","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMastocytosis encompasses a group of rare disorders characterized by abnormal proliferation of mast cells in one or more organs. Clinical expression is highly variable and depends both on mast‑cell mediator release and tissue infiltration. Gain‑of‑function somatic mutations of the KIT gene are identified in more than 80% of pediatric mastocytosis cases (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). In children, cutaneous involvement is the most common manifestation. According to the WHO classification, cutaneous mastocytosis is divided into three clinical forms (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Urticaria pigmentosa is the most frequent form, accounting for approximately 65% of cases (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e), while solitary mastocytoma is observed in 9\u0026ndash;35% (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Diffuse forms, such as bullous mastocytosis, are much rarer but may lead to more severe symptoms. This clinical diversity may complicate diagnosis and highlights the importance of reporting rare or atypical cases. The present case illustrates a particular manifestation of this disease, providing further insight into its clinical variability.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eWe report the case of a 9‑month‑old female infant from Sfax with no significant past medical history, admitted to the pediatric intensive care unit for management of extensive oozing epidermal detachment. Symptoms began five days prior to admission with a flu‑like syndrome, followed by the appearance of an erythematous rash involving the thorax, trunk, and all four limbs, which rapidly progressed to bullous detachment within 24 hours \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. A history of symptomatic treatment with paracetamol and homeopathic remedies was reported. Due to the severity and extent of skin lesions associated with respiratory deterioration, the patient was admitted to the intensive care unit. She was febrile, tachypneic with hoarseness, and hemodynamically stable. Dermatological examination revealed areas of epidermal detachment with a \u0026lsquo;wet sheet\u0026rsquo; appearance; Darier\u0026rsquo;s sign was positive in the axillary folds, neck folds, and back. The background skin was ecchymotic with hemorrhagic bullae overlying ecchymotic areas, particularly on the neck \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e There was no mucosal or diaper area involvement. The scalp was also affected \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003eInitial laboratory investigations showed an inflammatory response with CRP of 45 mg/L, leukocyte count of 9,930/mm\u0026sup3;, and eosinophils at 20%. Upon admission, the patient was intubated and mechanically ventilated due to respiratory distress. Skin care included sterile wet dressings, paraffin gauze, and petroleum jelly, along with systemic dexamethasone. Toxic epidermal necrolysis and staphylococcal scalded skin syndrome were initially suspected, prompting treatment with intravenous immunoglobulins for two days and antibiotics (teicoplanin combined with amoxicillin\u0026ndash;clavulanic acid). Skin swab cultures revealed various staphylococcal species.\u003c/p\u003e \u003cp\u003eOn day two of hospitalization, bullous mastocytosis was suspected based on the infiltrated yellowish plaques on the flank, glottic edema, and respiratory distress. Serum tryptase level was markedly elevated at 73.7 \u0026micro;g/L (normal\u0026thinsp;\u0026lt;\u0026thinsp;8.4 \u0026micro;g/L). The diagnosis of diffuse cutaneous mastocytosis was confirmed by skin biopsy showing a thin epidermis with parakeratotic scales and intra‑ and subepidermal micro‑abscesses. The underlying dermis contained a dense band‑like inflammatory infiltrate composed predominantly of confluent sheets of mast cells, with scattered eosinophils and neutrophils. Immunohistochemistry demonstrated intense and diffuse CD117 staining. The patient was treated with topical hydrocortisone, antiseptic cream, and oral antihistamines.\u003c/p\u003e \u003cp\u003eThe hospital course was complicated by suspected care‑related infection requiring clindamycin, and by right internal jugular vein thrombosis. Skin condition improved within days of treatment, with re‑epithelialization, reduced erythema, and absence of new bullae \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e The patient was discharged home after 20 days of hospitalization, including 11 days in intensive care and 7 days of mechanical ventilation. Parents received education on trigger avoidance and follow‑up care. At 7‑month follow‑up, complete resolution of lesions was observed \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e \u003cb\u003e).\u003c/b\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe prevalence of pediatric mastocytosis is estimated at 1 to 10 cases per 100,000 individuals (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Between 60% and 80% of patients develop skin lesions during the first year of life (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). In children, most cases are benign, and the cutaneous form is the most frequent. Based on the clinical appearance of skin involvement, cutaneous mastocytosis (CM) is divided into three main forms: maculopapular cutaneous mastocytosis (MPCM), also known as urticaria pigmentosa; diffuse cutaneous mastocytosis (DCM); and cutaneous mastocytoma (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMPCM is the most common form and presents as red-brown macules or slightly elevated papules measuring 0.5 to 1 cm, predominantly involving the trunk and extremities, while the face, scalp, palms, and soles are generally spared (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Mastocytoma is characterized by a nodular or plaque-like lesion, solitary or up to a maximum of three lesions. DCM is a rare and severe form, and its bullous variant is an extremely rare entity, with an estimated occurrence of 1 per 1,000,000 individuals (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). It usually presents at birth (congenital or infantile form) or during early childhood (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Clinically, it manifests as erythroderma and pachydermia, with thickened, leathery skin showing an \u0026ldquo;orange peel\u0026rdquo; appearance due to mast cell infiltration, associated with bullae and blisters (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). A positive Darier\u0026rsquo;s sign is pathognomonic for all forms of CM (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Pruritus is frequently present (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e), and hyperpigmentation may persist into adulthood. Other systemic symptoms, such as flushing and gastrointestinal disturbances, may occur as a result of histamine and other mast cell mediator release into the bloodstream (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn our case, toxic epidermal necrolysis (Lyell syndrome) or a staphylococcal skin infection was initially suspected before the diagnosis of bullous mastocytosis was established. Indeed, the clinical presentation may resemble Stevens\u0026ndash;Johnson syndrome/toxic epidermal necrolysis or other pediatric bullous disorders, including staphylococcal scalded skin syndrome, linear IgA bullous dermatosis, epidermolysis bullosa, bullous impetigo, and bullous erythema multiforme (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). The clinical manifestations of bullous diseases in children are often very similar, making clinical diagnosis challenging. Roux et al. (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) reported a similar case that was initially diagnosed and treated as Stevens\u0026ndash;Johnson syndrome, with the diagnosis of bullous mastocytosis subsequently confirmed by skin biopsy.\u003c/p\u003e \u003cp\u003eThe vast majority of mastocytosis cases result from a somatic mutation of the proto-oncogene c-KIT (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e), which encodes the KIT receptor, also known as CD117, a tyrosine kinase receptor responsible for mast cell differentiation, maturation, and proliferation (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Mutations in c-KIT lead to constitutive activation of the KIT receptor, resulting in mast cell proliferation within tissues (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Sotlar et al. reported c-KIT gene mutations in skin biopsies from 16 of 37 pediatric patients (43%) with cutaneous involvement (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe diagnosis of cutaneous mastocytosis is often challenging and relies on a combination of clinical and biochemical findings (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Initial evaluation includes a complete clinical and dermatological examination, complete blood count, blood biochemical tests, and serum tryptase measurement, as well as skin biopsy with histological examination. Tryptase is a serine protease primarily synthesized and stored in mast cells (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Baseline serum tryptase levels reflect the total mast cell burden of the body, making it useful for the diagnostic workup and follow-up of systemic mastocytosis. A baseline serum tryptase level greater than 20 ng/mL is defined by the WHO as a minor diagnostic criterion for systemic mastocytosis (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e), particularly when associated with cytopenias and organomegaly (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). However, elevated tryptase levels may strongly suggest the diagnosis without definitively confirming it. Several other conditions are associated with elevated baseline serum tryptase levels, including hereditary alpha-tryptasemia, allergic diseases, chronic eosinophilic leukemia, and certain nephropathies (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn our case, serum tryptase levels were elevated in the absence of other signs of systemic involvement. Elevated serum tryptase levels are commonly observed in patients with extensive skin involvement, particularly those with diffuse cutaneous mastocytosis (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). The diagnostic gold standard relies on formalin-fixed skin biopsy with CD117 immunostaining, demonstrating significant dermal infiltration by mast cells (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). The major histological criterion for diagnosis, with a specificity\u0026thinsp;\u0026ge;\u0026thinsp;95%, is a mast cell density greater than 139 mast cells/mm\u0026sup2; in the superficial dermis (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). However, skin biopsy is not systematically required and is mainly indicated in doubtful cases, when Darier\u0026rsquo;s sign is not evident or when skin lesions are atypical (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Genetic analysis for activating KIT mutations in skin and peripheral blood is particularly important in uncertain cases, as it represents the most specific criterion for cutaneous mastocytosis lesions. Determination of KIT D816V mutational status using highly sensitive quantitative real-time PCR is recommended (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTo date, no curative pharmacological treatment exists for mastocytosis (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). The main goal of cutaneous mastocytosis management is to reduce and control mast cell mediator release (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). The first and most important preventive measure is avoidance of triggering factors. Numerous environmental and pharmacological factors may induce mediator release, including extreme temperatures (heat and cold), fever, infections, stress, physical exercise, skin friction, nonsteroidal anti-inflammatory drugs, opioids, contrast agents, dextromethorphan, and certain antibiotics such as quinolones (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). This highlights the importance of parental education prior to discharge and during follow-up visits. In our case, paracetamol was not considered a risk medication, but a preceding infection may have acted as the triggering factor. The use of an epinephrine auto-injector in cases of severe hypotension or shock is recommended, particularly in children with extensive skin involvement, a history of severe systemic symptoms or anaphylaxis, and markedly elevated serum tryptase levels.\u003c/p\u003e \u003cp\u003eSymptomatic treatment of diffuse cutaneous mastocytosis can be achieved under sterile conditions through the application of topical therapies and oral medications, such as topical corticosteroids or topical sodium cromoglycate, and oral antihistamines (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). The use of systemic corticosteroids is limited by their numerous side effects but may be indicated for short durations in cases of extensive lesions and recurrent bullae (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Refractory cases may be treated with omalizumab (an anti-IgE monoclonal antibody) or psoralen plus ultraviolet A photochemotherapy (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Follow-up is recommended every 6 to 12 months. Parents should be informed of the rare possibility of progression to systemic disease (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). A recent literature review showed that approximately 1 in 100 children with cutaneous mastocytosis may develop a systemic form (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDuring follow-up, our patient experienced an episode of wheezing dyspnea. Disease evolution may be characterized by complete absence of symptoms or, conversely, by the occurrence of mediator-related symptoms such as pruritus, flushing, bullae, wheezing, abdominal pain, diarrhea, hypotension, headaches, and depression (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). In general, most pediatric patients with cutaneous mastocytosis experience spontaneous regression around puberty and have a favorable prognosis (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e), despite a reported mortality rate of up to 24%, mainly due to anaphylactic shock and gastrointestinal hemorrhage (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). A recent prospective study evaluating the long-term outcome of pediatric mastocytosis in 28 children reported diffuse bullous involvement in 6% of cases, with a favorable outcome observed in 25% of those patients (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePediatric bullous mastocytosis is a rare and underdiagnosed condition. Early recognition relies on careful correlation of clinical, histopathological, and biological findings. Identification of Darier\u0026rsquo;s sign, CD117‑positive mast‑cell infiltration, and elevated serum tryptase are essential for diagnosis. Symptomatic management is usually effective, but vigilant monitoring remains necessary given the potential for severe systemic manifestations.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The study was conducted in accordance with ethical standards, and ethical principles were fully respected.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Informed written consent was obtained from the parents of the patients for publication of the paper and all informations within it. The proof of consent can be requested at any time\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The authors received no specific funding for this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;All authors contributed to the study conception, data collection, analysis, and manuscript preparation. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The authors would like to thank all participants and collaborators who contributed to this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePolivka L, Bodemer C. Mastocytose p\u0026eacute;diatrique. Horizons H\u0026eacute;mato. 2018.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eValent P, Akin C, Metcalfe DD. Mastocytosis: 2016 updated WHO classification and novelemergingtreatment concepts. Blood 16 mars. 2017;129(11):1420\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBen-Amitai D, Metzker A, Cohen HA. Pediatriccutaneousmastocytosis:areview of 180 patients. 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The Normal Range of Baseline Tryptase Should Be 1 to 15 ng/mL and CoversHealthyIndividualsWith HαT. J Allergy Clin ImmunolPract oct. 2023;11(10):3010\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCarter MC, Metcalfe DD, Komarow HD, Mastocytosis. ImmunolAllergy Clin North Am f\u0026eacute;vr. 2014;34(1). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.iac.2013.09.001\u003c/span\u003e\u003cspan address=\"10.1016/j.iac.2013.09.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRydz A, Lange M, Ługowska-Umer H, Sikorska M, Nowicki RJ, Morales-Cabeza C, et al. Diffuse CutaneousMastocytosis: A CurrentUnderstanding of a Rare Disease. Int J Mol Sci 23 janv. 2024;25(3):1401.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eŁugowska-Umer H, Czarny J, Rydz A, Nowicki RJ, Lange M. Current Challenges in the Diagnosis of PediatricCutaneousMastocytosis. Diagnostics. 1 d\u0026eacute;c2023;13(23):3583.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGebhard J, Horny HP, Kristensen T, Broesby-Olsen S, Zink A, Biedermann T, et al. Validation of dermatopathologicalcriteria to diagnose cutaneouslesions of mastocytosis: importance of KIT D816V mutation analysis. J EurAcadDermatolVenereol JEADV ao\u0026ucirc;t. 2022;36(8):1367\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLange M, Niedoszytko M, Nedoszytko B, Łata J, Trzeciak M, Biernat W. Diffuse cutaneousmastocytosis:analysis of 10 cases and a brief review of the literature. J EurAcadDermatolVenereol JEADV d\u0026eacute;c. 2012;26(12):1565\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHartmann K, Escribano L, Grattan C, Brockow K, Carter MC, Alvarez-Twose I, et al. Cutaneous manifestations in patients withmastocytosis: Consensus report of the EuropeanCompetence Network on Mastocytosis; the American Academy of Allergy, Asthma\u0026amp;Immunology and the EuropeanAcademy of Allergology and ClinicalImmunology. J Allergy Clin Immunol janv. 2016;137(1):35\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePopadic S, Lalosevic J, Lekic B, Gajić-Veljic M, Bonaci-Nikolic B, Nikolic M. Mastocytosis in children:a single-center long-term follow-up study. Int J Dermatol. 2023;62(5):616\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Diffuse cutaneous mastocytosis, bullous dermatosis, serum tryptase","lastPublishedDoi":"10.21203/rs.3.rs-8678247/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8678247/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMastocytosis is a rare disorder characterized by abnormal proliferation and accumulation of mast cells. In children, it is most often limited to the skin. Diffuse cutaneous mastocytosis is the rarest form and typically presents during infancy, frequently with extensive bullous lesions. Due to its rarity and clinical resemblance to other bullous dermatoses, early diagnosis remains challenging.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe report the case of a 9-month-old female infant admitted for an extensive pruritic bullous and ecchymotic eruption involving the thorax, limbs, and scalp. Physical examination revealed thickened infiltrated skin and a positive Darier’s sign, while mucous membranes were spared. Routine laboratory investigations were normal. Skin biopsy showed a dense subepidermal dermal infiltrate composed predominantly of mast cells arranged in confluent sheets. Immunohistochemical staining demonstrated strong and diffuse CD117 positivity. Serum tryptase levels were elevated, supporting the diagnosis of diffuse cutaneous mastocytosis. The patient was treated with topical corticosteroids, sterile dressings, and oral antihistamines, with complete resolution of skin lesions and no systemic complications.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDiffuse cutaneous mastocytosis should be considered in infants presenting with bullous skin lesions. Histological and immunohistochemical confirmation is essential for diagnosis. Although prognosis is generally favorable, careful follow-up is required due to the risk of severe mediator-related manifestations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number: not applicable\u003c/strong\u003e\u003c/p\u003e","manuscriptTitle":"Pediatric Bullous Mastocytosis: Diagnostic Challenges and Therapeutic Strategies","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-27 10:44:39","doi":"10.21203/rs.3.rs-8678247/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-03-14T12:23:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"190639459867561321723025038850412406724","date":"2026-03-01T10:02:48+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-24T07:22:27+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-30T13:35:09+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-29T08:34:53+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-29T08:33:10+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2026-01-23T10:20:08+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"87ae0bda-37b0-43c9-ad9a-cefb745a984d","owner":[],"postedDate":"February 27th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-27T10:44:39+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-27 10:44:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8678247","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8678247","identity":"rs-8678247","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}