A Case of Pediatric Indolent Systemic Mastocytosis: the Role of UVB‐NB Phototherapy in the Treatment of Cutaneous Lesions

Mastocytosis encompasses a heterogeneous group of disorders characterized by pathological expansion and accumulation of clonal mast cells within one or more organs.1 According to the latest classification, three subtypes of the disease have been recognized based on the site and extent of organ involvement and dysfunction: cutaneous mastocytosis (CM), systemic mastocytosis (SM), and mast cell sarcoma (MCS).2, 3 SM has been differentiated into non-advanced and advanced forms, while the CM is divided into maculopapular CM (MPCM), diffuse CM (DCM), and mastocytoma subtypes.2, 3 In pediatric age, mastocytosis is often limited to the skin (CM) and is considered to be a myeloproliferative clonal disease with benign course, outcome, and tendency to spontaneous resolution before puberty.4 Extracutaneous involvement in pediatric mastocytosis is relatively rare, most often presenting in the form of indolent systemic mastocytosis (ISM). Virtually all children with SM present with skin lesions, usually MPCM, accompanied by increased serum tryptase levels.4 Currently, the treatment of SM in pediatric patients lacks of standard guidelines: its primary aim is to limit the release of mediators of mast cell degranulation, by avoiding potential triggering factors. The mainstay of systemic therapy is second-generation H1 and H2 anti-histamines, useful in decreasing flushing, pruritus, and controlling wheal formation.1, 5 A valuable second-line therapy, proposed as an alternative approach for the treatment of refractory cases, is phototherapy.6 UVB-NB phototherapy has been shown to be effective in many dermatological pediatric diseases associated with intense itch,7, 8 and UVB light has been proven to have an inhibitory effect on mast cell degranulation, likely by causing noncytotoxic damage to the membrane phospholipid metabolism.9, 10 Omalizumab has been successfully used to treat severe symptoms related to mastocytosis that are recalcitrant to conventional therapies,11 including cases of CM and ISM in pediatric patients,12 while in case of aggressive SM the clinician can consider the use of imatinib (if mast cells lack the c-KIT D816V mutation) or other newer tyrosine-kinase inhibitors.13 We report a case of a 13-year-old girl, affected by ISM, who presented with cutaneous lesions since the sixth month of life, successfully treated with UVB-NB phototherapy. The patient initially received a diagnosis of MPCM, and was referred to our Dermatologic Institute due to progressive worsening of her skin lesions during adolescence. At that time, she presented with several papules and erythematous, brown macules distributed on her face, arms, and trunk, and positivity for Darier's sign. Pruritus was one of the greatest causes of discomfort for the patient. The disfiguring appearance of the skin lesions was correlated with body image concerns, deeply affecting her quality of life (Figure 1). A progressive increase in the serum tryptase values was observed (from the baseline value of 24 ng/mL to 41.3 ng/mL. NV ≤11.5 ng/mL), raising the suspicion of a possible multiorgan involvement and evolution to SM. Skin biopsy was repeated, confirming hyperpigmentation of basal layer of epidermis with diffuse mast cell infiltrates with monomorphous mononuclear cells, round to oval nuclei, granular amphophilic cytoplasm, tryptase, and CD117 positive. A bone marrow biopsy showed the presence of >15 MCs with the coexpression of CD2, CD25, and CD117 at flow cytometry analysis. The c-KIT D816V mutation, tested with PCR/RFLP assay, was also positive. FDG-PET scan did not show pathologic hypercaptation. Lumbar bone mass densitometry displayed a Z-score below the expected range for age (−2.1). A diagnosis of ISM was made. The patient was initially treated with topical corticosteroids and second-generation anti-histamines. Nevertheless, symptoms and pruritus control remained unsatisfactory. The psychological and social impact of the skin disease was still unsolved. Phototherapy with UVB-NB was initially introduced twice weekly on nonconsecutive days. A UV irradiation cabin equipped with 8 Philips TL-01″ fluorescent UVB lamps with a peak emission at 311–313 nm was used. The starting dose of UVB-NB was determined according to the patient's skin type (Fitzpatrick scale). Considering the possibility of massive mast cell degranulation, a safer irradiation protocol was employed. At each session the dose of irradiation was increased by 10% if there were no signs of erythema. UVB-NB therapeutic regimen was continued, if no treatment-related side effects occurred, until an optimal control of cutaneous lesions and a significant reduction of pruritus was achieved. Subsequently, irradiation was tapered by decreasing the frequency of treatment. The patient underwent a total of 30 treatments with a cumulative dose of 24.8 J/cm2 over the course of 3 months, achieving a complete resolution of the skin lesions and remission of pruritus (Figure 2), with no recurrences after 6 years of follow-up. Systemic involvement remained stable, as demonstrated by minimal increase in tryptase levels and stability of the Z-score. Our results did not evidence a significant decrease in tryptase levels after treatment discontinuation, suggesting that tryptase monitoring does not correlate with the expressivity of cutaneous manifestations. Previous reports on the efficacy of UVB-NB in mastocytosis have mostly focused on MPCM/UP in the adult age,6, 13 while only a single report on the use of UVB-NB in ISM in adolescents has been published to date14; to our knowledge, this case is the first to describe the efficacy of UVB-NB in a pediatric case of ISM. Our pediatric data confirm those obtained in adulthood both on the reduction of itching and on the clinical response with disappearance/reduction of skin lesions. As in adult population, phototherapy did not affect tryptase levels.6, 13, 14 This case illustrates that UVB-NB phototherapy shows promising results and it could be considered as an important second-line therapy to treat cutaneous symptoms in pediatric mastocytosis patients, especially when other regimens have failed.13 Further prospective studies are needed in order to investigate the potential of this technique, the most optimal treatment regimen and dosing, and its possible drawbacks. We thank the nurses of the Institute of Dermatology, Fondazione Policlinico San Matteo IRCCS Pavia Anna M. and Anna P. for their invaluable contribution to this study. Open access funding provided by BIBLIOSAN. None to declare. The patient provided written informed consent to the publication of her case details. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.