Selective Response to Omalizumab in a Patient With Concomitant ncMCAS and POTS: What Does it Teach us About the Underlying Disease?

Abstract

261Investigations at the time showed no evidence of an allergic disorder. However, serum mast cell tryptase levels were periodically elevated, ranging from 10 mg/mL to 20 ng/mL between attacks, but increasing to >100 ng/mL following episodes of anaphylaxis. Subsequent investigations to exclude a clonal mast cell disorder were performed in another center. This included a complete bone marrow study to assess the number of mast cells and typical histological lesions of systemic mastocytosis, such as multifocal dense, sharply demarcated mast cell infiltrates [5]. Furthermore, bone marrow aspirate was examined for the number of mast cells and their morphological features, and immunophenotyping studies were performed to assess expression of CD2 and CD25, which are typically found on mast cells from patients with systemic mastocytosis [5]. Lastly, cKIT mutation analysis yielded negative results; however, we do not know if this was performed from purified mast cells, as currently recommended [6]. Altogether, these investigations showed no evidence of clonal mast cell proliferation.Blood tests including measurements of plasma levels of epinephrine, aldosterone, rennin, 5-hydroxyindoleacetic acid (5-HIAA), and gut hormones were all normal. An extensive autoantibody screen for POTS-related autoantibodies was negative. This included anti-α-1 adrenergic, anti-α-2 adrenergic, anti-β-1 adrenergic, and anti-β-2 adrenergic receptor antibodies, as well as antimuscarinic cholinergic receptor 1, 2, 3, 4, and 5 antibodies. The patient and close family members (mother, father, and a brother) underwent further genetic tests. Although there was no family history of ncMCAS/POTS, the severity and early onset of the patient's illness led us to consider a monogenic cause of this rare clinical phenotype. However, whole exome sequencing carried out on the patient's DNA failed to reveal an obvious genetic cause.The patient received numerous treatments for ncMCASrelated symptoms, including high-dose H 1 nonsedating antihistamines, H 2 antihistamines, montelukast, sodium cromoglycate, and the tyrosine kinase receptor inhibitor imatinib, which is an effective inhibitor of wild-type KIT; however, it is currently indicated for treatment of systemic mastocytosis with imatinib-sensitive KIT mutations only [7]. Considering that imatinib might cause potentially dangerous adverse effects, it is not recommended for routine use in ncMCAS. In this case, the permission to use imatinib was obtained from the hospital's Drugs and Therapeutics Committee, and appropriate consent was obtained from the patient prior to commencing the treatment. Unfortunately, none of the medications were fully effective, resulting in only partial improvement of the patient's condition. He also tried several medications to control his POTS-related symptoms. These included moxonidine and amlodipine for hypertension, pyridostigmine for orthostatic hypotension, pregabalin for erythromelalgia, and propantheline for hyperhidrosis. These drugs were discontinued owing to lack of effect (...

Post-HPV-Vaccination Mast Cell Activation Syndrome: Possible Vaccine-Triggered Escalation of Undiagnosed Pre-Existing Mast Cell Disease?

“…Although no causative linkages have yet been identified, tentative associations between MCAS and a rapidly widening range of co-morbidities [33,60], including POTS [36,[61][62][63][64][65][66], have been identified, though none yet have been particularly well-characterized. Although neither the symptom of lightheadedness nor the diagnosis of presyncope is equivalent to a diagnosis of POTS, two studies of independent large cohorts of MCAS patients found an identical prevalence (71%) of lightheadedness or presyncope [33,67].…”