A successful treatment of urticaria pigmentosa with omalizumab in a pediatric patient: a case report

Introduction

Mastocytosis is a rare and heterogeneous myeloproliferative disorder characterized by the abnormal proliferation and/or accumulation of mast cells in various tissues, divided into systemic and cutaneous mastocytosis (CM) (1). CM is confined to the skin and further subdivided into maculopapular CM (urticaria pigmentosa), mastocytomas of the skin, and diffuse CM (1). However, standard therapeutic approaches for CM aim to mitigate the symptoms associated with the release of mast cell-derived mediators (1). One promising therapeutic option is the monoclonal antibody omalizumab (1). Here, we present a paediatric case of CM with significant clinical improvement following omalizumab treatment. We present this article in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-207/rc).

Case presentation

A 14-year-old female adolescent of Middle Eastern ethnicity, without any known chronic medical conditions, presented to our secondary care facility with a chief complaint of intensely pruritic, hyperpigmented macules that had persisted for 1 year affecting her sleep, schooling, and quality of life. The cutaneous lesions were distributed across the patient’s body, with a predominance in the acral regions. Family history was unremarkable.

Physical examination revealed widespread excoriated erythematous and brown macules on the right arm (Figure 1) and hyperpigmentation with occasional excoriation marks on the legs (Figure 2). A positive response was elicited by performing Darier’s sign. Abdominal examination did not reveal hepatosplenomegaly, and there were no clinical features suggestive of systemic mastocytosis.

Figure 1 Multiple scattered erythematous and brown macules on the right arm.

Figure 2 Hyperpigmentation with occasional excoriation marks on the legs.

Initial differential diagnoses included urticaria (2), urticarial vasculitis, CM (1), insect bite reaction, hereditary disorders, and autoimmune conditions. Diagnostic reasoning for exclusion of differential diagnoses proceeded as follows: Urticaria was excluded because the lesions were persistent throughout the 1-year duration rather than demonstrating the typical transient, on-and-off pattern characteristic of urticaria (2). Urticarial vasculitis was ruled out as the lesions were erythematous and brown macules without purpuric features. Insect bite reactions were excluded due to the chronic 1-year history (rather than acute, short-term presentation) and the widespread, symmetric distribution pattern rather than punctate, localized lesions typical of arthropod bites. Hereditary and autoimmune conditions were considered less likely given the negative family history and clinical presentation, though complete workup was performed.

After thorough investigations, a 4-mm punch biopsy from the right forearm, stained with hematoxylin-eosin (H&E) saffron, showed a keratinized epidermis with mild perivascular lymphoplasmacytic inflammation in the superficial dermis and pigmentary incontinence (Figure 3) and scattered mast cells positive for CD117 (Figure 4).

Figure 3 Hematoxylin-eosin saffron stain microphotograph showing a skin punch biopsy with keratinized epidermis, superficial dermal mild perivascular lymphoplasmacytic inflammation and pigmentary incontinence (original magnification: ×400).

Figure 4 Immunohistochemical staining method for CD117 (c-Kit) demonstrating scattered mast cells with brown cytoplasmic positivity (×40).

Additional laboratory investigations, including complete blood count, antinuclear antibodies, inflammatory markers, virological studies, and serum tryptase level, were all within normal limits. Total immunoglobulin E (IgE) was mildly elevated at 217 IU/mL; IgE was measured as part of the comprehensive workup to exclude other IgE-mediated allergic conditions in the differential diagnosis, including atopic dermatitis and food allergies. Based on the clinicopathological correlation, positive Darier’s sign, CD117-positive mast cells on histopathology, and absence of systemic features, the patient was diagnosed with CM.

Conventional management for CM, including H1-antihistamines (fexofenadine and cetirizine), topical and systemic corticosteroids (betamethasone), and Montelukast, led to only mild improvement. Despite increasing the antihistamine dose to four times daily, the patient continued to experience recurrent urticarial attacks with facial swelling and intensely itchy wheals. During the initial 6-month period of conventional therapy, the patient required three courses of oral prednisone (15 mg once daily for 2 weeks each) to manage acute flares and relieve the severity of symptoms.

Given the inadequate response to conventional therapy, the decision was made to initiate treatment with omalizumab at a dose of 150 mg administered subcutaneously monthly. To monitor for potential adverse events, particularly anaphylaxis, omalizumab was administered in a clinical setting with full resuscitation equipment and trained personnel available. The patient was observed for 3 hours following each injection, particularly during the initial doses. However, as the patient continued to experience relapsing urticarial attacks after 2 months on this initial dose, the omalizumab dose was increased to 300 mg monthly.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the parents of the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Treatment outcomes and follow-up

Upon close monitoring, the patient showed remarkable improvement, with resolution of residual lesions and absence of disease flare-ups. Objective assessment using the Dermatology Life Quality Index (DLQI) showed significant improvement from a baseline score of 23 (indicating very large effect on patient’s life) to a score of 2 at the most recent follow-up (indicating minimal impact on quality of life). The patient was able to resume her daily activities, sleep well, and participate fully in her school life.

The patient has been followed for 2 years since omalizumab initiation. After achieving complete symptom control on 300 mg monthly for 1 year, the dose was successfully tapered to 300 mg every 2 months for 6 months, and is currently maintained on 150 mg every 2 months. The patient has remained completely asymptomatic throughout this entire 2-year period, with stable serum tryptase levels and CD63 counts. No adverse events related to omalizumab have been observed during the entire treatment course. A detailed clinical timeline of key events is provided in Table 1.

Patient perspective

The patient and her family reported that prior to omalizumab therapy, the intense pruritus significantly impacted every aspect of her life. The patient described being unable to sleep through the night due to constant itching, which led to daytime fatigue and difficulty concentrating at school. She reported feeling self-conscious and embarrassed about the visible skin lesions, which affected her social interactions and self-confidence. Her mother noted that the patient frequently missed school during flare-ups and was unable to participate in normal teenage activities. Following successful omalizumab treatment, the patient expressed profound relief, stating that she could finally “feel normal again” without the constant discomfort and self-consciousness about her appearance. Both patient and family expressed gratitude for the dramatic improvement in quality of life.

Discussion

Current management of mastocytosis focuses on symptom relief and suppressing mast cell mediators (3). H1 and H2 antihistamines, alone or combined with corticosteroids, are the mainstay of treatment, but less than 50% of patients respond optimally to H1-antihistamine therapy (2,3). Montelukast is more effective than antihistamines but less so than omalizumab in the management of mastocytosis (2).

Omalizumab, a humanized monoclonal antibody targeting IgE, has emerged as a promising therapeutic option for refractory mastocytosis. The mechanism involves inhibiting IgE binding to high-affinity receptors (FcεRI) on mast cells and basophils, reducing FcεRI expression and thereby decreasing mast cell activation (4). While initially approved for allergic asthma and chronic urticaria, accumulating evidence supports its use in mastocytosis, particularly for refractory cases (5-12).

Evidence from adult literature

A 2020 systematic review by Jendoubi et al. analyzing 69 adult patients (13 with CM, 56 with systemic mastocytosis) found that omalizumab at 300 mg monthly for a mean duration of 17 months led to complete resolution of anaphylaxis in all patients with post-honeybee sting reactions and complete resolution of idiopathic anaphylaxis in 84% of cases (5). Complete symptom resolution rates were: palpitations 43%, gastrointestinal symptoms 29%, cutaneous symptoms 27%, neuropsychiatric 11%, and respiratory 9% (5). A 2024 systematic review of CM specifically found that 95% of adult patients showed improvement, with three achieving complete remission within an average of 4 months, though 16% experienced relapse (6). More recent evidence from a 2025 systematic review of mast cell activation syndrome showed that 61% of patients had partial response and complete response was more common with higher doses (≥300 mg/month) (7).

Pediatric literature

The pediatric literature on omalizumab in mastocytosis, while limited, demonstrates particularly encouraging results. Bossi et al. [2023] reported the second pediatric case of systemic mastocytosis treated with omalizumab, where a child became completely asymptomatic after only two doses of 300 mg (8). Their comprehensive literature review revealed that among published cases up to 2023, only 5 of 81 (6%) patients treated with omalizumab were under 18 years (8). The 2024 systematic review analyzing pediatric-specific data found that all pediatric patients with CM experienced complete remission within an average of 1.5 months, with corticosteroid cessation achieved in 80% and no major adverse events reported, though 20% experienced relapse (6). Hughes et al. [2018] demonstrated effectiveness in very young children with severe CM (9), and a 2024 review by Chang et al. identified five additional pediatric cases achieving complete symptom resolution in an average of 2 months (10).

Current case

In our case, the patient’s condition did not respond adequately to conventional therapies, including H1-antihistamines (fexofenadine and cetirizine at four times daily dosing), topical and systemic corticosteroids, or Montelukast, requiring three courses of systemic prednisone pulses over 6 months. This therapeutic escalation parallels reported patterns in the literature where Omalizumab is reserved for refractory cases (5-8).

Consistent with the case series by Slapnicar et al. (11), our patient was initiated on 150 mg monthly, then escalated to 300 mg monthly due to continued relapses after 2 months. This dose adjustment strategy aligns with evidence that higher Omalizumab doses (≥300 mg/month) correlate with better complete response rates (7). The sustained symptom control achieved at 300 mg monthly for 1 year, followed by successful tapering to 300 mg every 2 months for 6 months, and ultimately to the current maintenance dose of 150 mg every 2 months, demonstrates both the efficacy and durability of response. Objective assessment documented DLQI improvement from 23 (very large impact) to 2 (minimal impact), supporting the substantial quality-of-life benefit observed in systematic reviews (5,6).

Tryptase levels and mechanistic insights

An interesting finding in our case was that serum tryptase levels remained stable throughout the 2-year treatment period despite excellent clinical improvement. This contrasts with Slapnicar et al.’s series where four of six patients demonstrated decreased tryptase (ranging from 11–40% reductions) (11). However, stable tryptase with clinical improvement has been reported in other pediatric cases (8,10), suggesting heterogeneity in omalizumab’s mechanism of action. This discrepancy may indicate that in some patients, omalizumab operates primarily through mast cell stabilization, reducing mediator release and activation, rather than reducing overall mast cell burden (reflected by tryptase levels). This mechanistic distinction has important implications: patients with stable tryptase may require continued therapy for mast cell stabilization, while those with decreased tryptase might achieve more durable remission allowing treatment discontinuation. Further research is needed to identify patient-specific factors that determine which mechanism predominates and whether tryptase response can guide treatment duration.

Safety profile

Throughout the 2-year treatment course with comprehensive monitoring including 3-hour post-injection observation periods, our patient experienced no adverse events. This excellent safety profile is consistent with the pediatric systematic review showing no major adverse events in children (6) and the broader literature demonstrating favorable tolerability (5-10). Notably, adverse events requiring treatment discontinuation, while reported in adult series (5,11), remain rare. The steroid-sparing effect observed in our patient, elimination of the need for systemic prednisone pulses represents a significant clinical benefit given the well-documented adverse effects of chronic corticosteroid use in pediatric patients (8).

Study strengths and limitations

A key strength of this report is that it documents the first pediatric case of CM in Saudi Arabia successfully treated with Omalizumab, adding to the scarce literature on pediatric presentations. The inclusion of objective outcome measures (DLQI scores), detailed treatment timeline, extended 2-year follow-up with successful dose tapering, and comprehensive safety monitoring strengthen the clinical evidence. A limitation is that it is a single case report, so generalizability is limited. Additionally, the patient’s age (14 years) places her within the timeframe when pediatric CM can occasionally undergo spontaneous resolution around puberty; however, the 2-year sustained response including successful dose tapering, dramatic DLQI improvement, and temporal correlation with Omalizumab initiation support therapeutic efficacy rather than natural disease course alone. Another limitation is that H2-antihistamines were not trialed as part of the conventional therapy regimen before escalating to biologic treatment.

Conclusions

This case demonstrates that Omalizumab represents a highly effective and safe therapeutic option for pediatric patients with refractory CM who fail conventional management. Our patient achieved complete symptom resolution and sustained clinical remission over a 2-year follow-up period, with documented quality of life improvement from a DLQI score of 23 to 2, while avoiding chronic corticosteroid use. The successful dose optimization strategy, from 150 to 300 mg monthly followed by gradual tapering to a maintenance dose of 150 mg every 2 months, highlights the importance of individualized treatment approaches. As the first documented pediatric CM case in Saudi Arabia successfully treated with omalizumab, this report adds valuable evidence to the limited pediatric literature and supports omalizumab as a viable second-line therapeutic option when conventional treatments fail. However, the scarcity of pediatric data underscores the urgent need for well-designed clinical trials to establish evidence-based dosing guidelines, identify predictive biomarkers for treatment response, and determine optimal treatment duration for this promising biologic therapy in pediatric CM.

Acknowledgments

We would like to thank all participants for their collaboration and participation that helps to enrich the knowledge and information of the clinical community.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-207/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-207/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-207/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the parents of the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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