Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults

Journal of Allergy and Clinical Immunology (JACI) 127 (1), 72-80.e2 (Jan 2011)

Nelson HS, Nolte H, Creticos P, Maloney J, Wu J, Bernstein DI 

BACKGROUND Immunotherapy for allergic rhinoconjunctivitis (ARC) in North America is generally administered subcutaneously, but alternative formulations might be safer and more convenient. Trials of sublingual formulations in North America are needed to confirm European efficacy and safety data. 

OBJECTIVEWe sought to investigate the efficacy and safety of timothy grass allergy immunotherapy tablet (AIT) treatment in North American subjects with ARC. 

METHODS Four hundred thirty-nine adults with grass pollen-induced ARC with or without asthma were randomized to once-daily 2,800 bioequivalent allergen units of standardized grass AIT (oral lyophilisate, Phleum pratense, 75,000 standardized quality tablet, containing approximately 15 μg of Phl p 5) or placebo approximately 16 weeks before the 2009 grass pollen season (GPS). The primary end point was the average total combined score of the daily symptom score and the daily medication score during the GPS. Rhinoconjunctivitis Quality of Life Questionnaire with standardized activities (RQLQ[S]) scores, Phl p 5-specific IgG4 levels, and IgE-blocking factor levels were additional end points. Adverse events (AEs) were monitored for safety. 

RESULTS Relative to placebo, grass AIT treatment improved total combined scores by 20% (P = .005), daily symptom scores by 18% (P = .02), and RQLQ(S) scores by 17% (P = .02). Daily medication scores were improved by 26% and trended toward significance (P = .08). Phl p 5-specific IgG4 and IgE-blocking factor levels were higher after grass AIT treatment compared with those after placebo at the end of the GPS (P <.001). Grass AIT treatment was safe and well tolerated. The majority of AEs were transient mild local reactions with no investigator-diagnosed grass AIT-related serious AEs or reports of anaphylactic shock/respiratory compromise. In the grass AIT group, 1 subject received epinephrine after experiencing a possible grade 1 systemic reaction (local site reactions, chest discomfort, and rash). 

CONCLUSIONS Timothy grass AIT treatment (cross-reactive with related Pooideae grasses) was demonstrated to be effective, generally safe, and well tolerated in North American adults with grass pollen-induced ARC.

Mucocutaneous leishmaniasis masquerading as Wegener granulomatosis

JCR: Journal of Clinical Rheumatology 16 (3), 125-8 (Apr 2010)

 

Brahn E, Pegues DA, Yao Q, Craft N;

 

A 43-year-old Brazilian female presented in 2001 with nasal stuffiness and sinusitis. A biopsy was consistent with limited Wegener's granulomatosis although antineutrophil cytoplasmic antibodies were negative. Her nasal inflammation progressed despite trials of prednisone, methotrexate, and azathioprine. A septal perforation developed and a repeat biopsy showed granulomatous inflammation. In 2006 the patient was referred to Division of Rheumatology, University of California, Los Angeles. 

The nose was grossly erythematous and a magnetic resonance imaging revealed nasal destruction and sinusitis. Palatine biopsies showed chronic inflammation. Cyclophosphamide at 150 mg/d resulted in markedly improved mucocutaneous lesions. The patient developed a leg and arm rash in 2007. A skin biopsy was positive for Leishmania braziliensis. The cyclophosphamide was discontinued and amphotericin B was initiated with transient benefit. Remission was achieved with pentavalent antimony. 

Despite multiple nasopharyngeal biopsies, for a 6-year span, mucocutaneous leishmaniasis masqueraded as Wegener's granulomatosis. Cyclophosphamide not only resulted in clinical improvement, due to reduced inflammatory response, but also allowed widespread cutaneous dissemination.

Autoimmune sialadenitis

Hals-Nasen-Ohrenheilkunde (HNO) (Mar 2010)

 Guntinas-Lichius O, Vissink A, Ihrler S

Using the European-American classification criteria the diagnosis of autoimmune sialadenitis in Sjögren's syndrome can generally be easily established or excluded. In addition, sonography performed by the ENT physician is helpful in diagnosing and especially in follow-up screening for MALT lymphomas, which 5%-10% of patients develop. Therapy of sicca symptoms is primarily symptomatic using substitution with fluids and stimulation with oral cholinergic drugs. Corticosteroids and/or antibiotics may play a role in patients with severe inflammatory episodes of autoimmune sialadenitis. Systemic therapy with immunomodulatory drugs such as azathioprine or cyclophosphamide is reserved for patients with extraglandular manifestations. However, the efficacy of this therapy is not proven by clinical studies. Rituximab, a new monoclonal CD20 antibody, seems to offer the first possibility of a causal therapy, under which the lymphoepithelial lesions in the salivary glands can disappear and saliva production improves. However, larger clinical studies are needed to evaluate the efficacy of this new therapy.

Optimal treatment of autoimmune sialadenitis requires interdisciplinary collaboration between ENT physician, oral and maxillofacial surgeon, rheumatologist, ophthalmologist, dentist, and pathologist.