Successful targeted treatment of mast cell activation syndrome with tofacitinib.

Mast cell (MC) activation syndrome (MCAS) is a collection of illnesses of inappropriate MC activation with little to no neoplastic MC proliferation, distinguishing it from mastocytosis. MCAS presents as chronic, generally inflammatory multisystem polymorbidity likely driven in most by heterogeneous patterns of constitutively activating mutations in MC regulatory elements, posing challenges for identifying optimal mutation-targeted treatment in individual patients. Targeting commonly affected downstream effectors may yield clinical benefit independent of upstream mutational profile. For example, both activated KIT and numerous cytokine receptors activate the Janus kinases (JAKs). Thus, JAK-inhibiting therapies may be useful against the downstream inflammatory effects of MCAS. The oral JAK1/JAK3 inhibitor, tofacitinib, is currently approved for rheumatoid arthritis and is in clinical trials for other chronic inflammatory disorders. Herein, we report two patients with MCAS who rapidly gained substantial symptomatic response to tofacitinib. Their improvement suggests need for further evaluation of this class of drugs in MCAS treatment.

Systemic reactions to subcutaneous allergen immunotherapy and the response to epinephrine.

The use of epinephrine for anaphylaxis to subcutaneous allergen immunotherapy (SCIT) is the standard of care, but its use for mild systemic reactions (SRs) is somewhat controversial. The objective of this study is to determine the rate of SR to SCIT, the symptoms reported, and the response to intramuscular (i.m.) epinephrine over a 1 year period. This retrospective study was designed to evaluate SRs to SCIT to any combination of approximately 20 allergens (pollens, animal emanations, molds, and Hymenoptera) in 773 subjects representing 14,707 visits, receiving approximately 28,000 injections over 1 year. Nurses were instructed to administer epinephrine (1:1000 v/v) 0.2 mL i.m. for signs or symptoms of a SR. SRs were graded using the universal grading system proposed by the World Allergy Organization (WAO) Joint Task Force for Grading SR to Immunotherapy. Thirty-one patients (4%) had 32 SRs, 22 (71%) female, average age 40 yr. Nineteen (61%) had a history of asthma; 7 (22.6%) had a history of a previous SR. SRs were reported on average 24 minutes after injection. Symptoms included: generalized pruritus, 34.4%; upper airway pruritus, 28.1%; cough, 25.0%; shortness of breath, 21.9%. Fourteen SRs were classified as Grade 1, thirteen Grade 2, two Grade 3, and three Grade 4. No Grade 5 or late phase reactions were reported. 29 (90.6%) reactions were treated with epinephrine, 27 (84.4%) glucocorticosteroid, and 30 (93.8%) H1 antihistamine. SRs occurred in 4% of patients receiving SCIT and all who received early intervention with epinephrine responded successfully. The WAO Grading system was useful.

Headache and facial pain: differential diagnosis and treatment.

Headaches affect 90% of the population sometime during their life. Most are benign and fleeting, some are serious and life-threatening, and others require ongoing medical consultation and treatment. A careful history and physical is necessary to establish a differential diagnosis and to guide the choice of testing to make an accurate diagnosis. The most common types of headaches are discussed in this review. They are divided into primary and secondary headache disorders as classified by the International Headache Society. Primary headache disorders include migraine without and with aura, cluster and tension-type headaches. Secondary headaches are those that occur as a result of some other disorder and include brain tumors, rhinosinusitis, diseases of intracranial and extracranial vasculature, and temporomandibular joint disease.

The impact of rhinosinusitis on asthma.

The nasal cavity, paranasal sinuses, and lungs are considered separate organs of the respiratory tract. However, a growing body of evidence links the upper and lower airways. For example, the coexistence and impact of allergic and nonallergic rhinitis on asthma is now documented. In addition, inflammation of the nose (rhinitis) commonly is associated with inflammation of sinuses (sinusitis), as reflected in the term rhinosinusitis. In this paper, we review the impact of rhinosinusitis on asthma as it relates to the links between allergic and nonallergic rhinitis and asthma; viral upper respiratory tract infections and asthma; allergic and nonallergic infectious/inflammatory rhinosinusitis and allergic and nonallergic hyperplastic rhinosinusitis and asthma; and the aspirin-exacerbated respiratory disease syndrome and asthma.