In the Italian Journal of Pediatrics, Bossi and colleagues reported the case of a pediatric patient with systemic mastocytosis (SM) who was successfully treated with omalizumab, adding to a growing body of evidence on the use of the asthma medication in treating SM.
An 8-year-old boy presented with what appeared to be an anaphylactic episode. He possessed all the hallmarks of this condition—general flushing, hypotension, and tachycardia, but with the absence of urticaria/angioedema. In addition, he had a persistently high tryptase value (27.5 ng/mL).
His only past medical history entailed a diagnosis of cutaneous mastocytosis (urticaria pigmentosa) made at 1 year of age; his skin lesions started to disappear spontaneously as he turned 5. He also had occasional episodes of flushing, bronchospasm, and gastrointestinal discomfort that self-resolved.
Upon his latest presentation, a physical examination was conducted, which was unremarkable. Due to his past diagnosis of cutaneous mastocytosis, his physicians conducted investigations based on the clinical suspicion that the disease had evolved to become systemic.
These investigations yielded a diagnosis of SM. The boy met 1 major World Health Organization (WHO) criterion and 2 minor ones: the presence of dense aggregates of mast cells in a bone biopsy, persistently elevated serum tryptase, and evidence of D816V point mutation in the c-KIT gene in a bone marrow biopsy. These observations, combined with the absence of any B- or C-findings, confirmed the diagnosis of indolent SM.
Read more about SM etiology
The first-line medications prescribed to the boy—antihistamines, cromolyn sodium, and topical steroids—did not ameliorate symptoms of his disease. Oral steroids only added to his adverse effects. Eventually, the child was forced to stop playing sports and withdraw socially.
“One year after the SM diagnosis, the first-line therapies’ failure was evident and we decided to treat our patient with omalizumab on compassionate use, keeping unchanged the current therapy,” Bossi and colleagues wrote. “Amazingly, the child became totally asymptomatic after the second dose of omalizumab.”
Twenty months later, the patient was completely symptom-free. He has not experienced any disease flare-ups. He was able to resume sporting activities and participate in school life. As a result of these improvements, the boy’s physicians planned to continue his omalizumab therapy.
“As far as we know, ours is the second pediatric case of SM successfully treated with omalizumab,” the authors of the report wrote.
An Off-Label Treatment With Big Effects
The case study presented in the Italian Journal of Pediatrics echoes that of another published in the Federal Practitioner in 2021. In the Federal Practitioner, Weiss and colleagues wrote about the case of a 32-year-old woman who was diagnosed with indolent SM and likewise received omalizumab treatment.
This patient was initially diagnosed with maculopapular cutaneous mastocytosis, as she presented with hyperpigmented macules and papules spread over her trunk and extremities. However, a bone marrow biopsy revealed prominent infiltrates of CD117+, CD2+, and CD25+ mast cells associated with reticulin fibrosis. This contributed to the diagnosis of indolent SM, which the WHO, among other criteria, defines as the presence of multifocal, dense aggregate of mast cells (>25%) in the bone marrow.
The woman was given 300 mg of omalizumab subcutaneously every 4 weeks; this treatment allowed her to experience only a single anaphylactic episode in 4 years. In addition, her cutaneous symptoms improved significantly.
The key similarity between the case reports was that omalizumab was prescribed off-label. The US Food and Drug Administration (FDA) has not incorporated SM as an indication for omalizumab. It is currently indicated only for severe, persistent asthma unresponsive to inhaled corticosteroids, as well as chronic idiopathic urticaria that remains symptomatic despite H1 antihistamine therapy.
“The main positive effect of omalizumab in adult patients with SM was the prevention of recurrent episodes of anaphylaxis, but also other symptoms, such as gastrointestinal complaints, asthenia, pruritus and flushing were positively affected,” Bossi and colleagues wrote. “Patients with [cutaneous mastocytosis] experienced reduction of skin symptoms.”
Read more about systemic mastocytosis treatment
In other words, omalizumab relieves some of the most vexing symptoms associated with SM. As Weiss and colleagues rightly pointed out in their case report, this therapy diminishes the “disease burden for patients with systemic mastocytosis who are otherwise limited to treatments aimed at transient symptomatic relief without significant alteration of the underlying cause of symptoms.”
Growing evidence from medical literature suggests that anti-IgE therapy addresses some fundamental aspects concerning the pathophysiology of diseases such as SM; it goes beyond being a short-term bandage meant to restrain symptoms until the next flare-up begins the vicious cycle anew.
SM, in all its various forms, is still an incurable disease. In such cases, physicians should prioritize reducing the disease burden and ensuring that quality of life is preserved. On both counts, omalizumab seems to perform with flying colors. If the body of literature expands to include further positive reports about the usage of omalizumab in SM, we can expect drug regulatory bodies to quickly take note.
Bossi G, Brazzelli V, De Amici M, et al. Successful treatment with omalizumab of a child affected by systemic mastocytosis: clinical and biological implications. Ital J Pediatr. 2023;49(1):6. doi:10.1186/s13052-022-01402-7
Weiss SL, Hyman JB, Carlson GS, Coop CA. Long-term successful treatment of indolent systemic mastocytosis with omalizumab. Fed Pract. 2021;38(1):44-48. doi:10.12788/fp.0081