Boaz Palterer

Neuromyelitis optica, atypical hemophagocytic lymphohistiocytosis and heterozygous perforin A91V mutation.

Neuromyelitis optica is an autoimmune demyelinating inflammatory disease characterized by optic neuritis and myelitis with anti-aquaporin 4 antibodies. Hemophagocytic lymphohistiocytosis is a severe systemic inflammatory syndrome that can present in a genetic primary form or secondarily to infective, neoplastic or autoimmune diseases. Our case discusses the first reported case of atypical late-onset hemophagocytic lymphohistiocytosis in a patient with neuromyelitis optica, with multiple triggering factors and carrying the common A91V hypomorphic perforin mutation, that blurs the distinction between primary and secondary forms.

Allergy and Sexual Behaviours: an Update

The exact prevalence of hypersensitivity reactions related to sexual behaviours is not known; however, they heavily impact on the quality of life and of sex life of affected patients. In fact, not only common respiratory and skin allergies, such as asthma, rhinitis, urticaria and atopic dermatitis, but also food and drug allergy have been found to negatively affect the quality of sex life. Allergic diseases impact on the sexual function in both physical and psychological ways, representing one of the main complaints of a considerable proportion of patients. Sexual behaviours may act as the triggers of allergic reactions or as the carriers of allergens. Food and drug allergens can be carried through human organic fluids, like saliva and semen. Latex in condoms and numerous substances in lubricants, spermicides, topical medications and cosmetics can cause allergic reactions or contact dermatitis. Sexual activity itself is also a potential trigger of symptoms in patients affected by respiratory allergies, like honeymoon asthma and rhinitis. In seminal plasma hypersensitivity, seminal fluid proteins are the culprit allergens. The present review aims at summarizing the state of the art about allergy and sexual behaviours. In clinical practice, the influence of common allergic diseases on the sexual quality of life should be taken carefully into account. Sexual behaviours need to be accounted in the differential diagnosis of hypersensitivity reactions, and awareness on those exposure routes should be raised between different specialists and general practitioners.

Reflex testing of speckled cytoplasmic patterns observed in routine ANA HEp-2 indirect immunofluorescence with a multiplex anti-synthetase dot-blot assay: a multicentric pilot study

Immunofluorescence on HEp2-cells is the standard diagnostic assay for the detection of anti-nuclear antibodies (ANA). Cytoplasmic speckled patterns are a common finding, and are associated with various antibodies, including anti-synthetase antibodies. However, classic ENA testing generally identifies only anti-Jo-1. Moreover, anti-synthetase syndrome is increasingly recognized as a pleomorphic entity, possibly presenting as isolated arthritis or interstitial lung disease. Sera referred for routine ANA testing were selected on the basis of the presence of a fine dense speckled cytoplasmic pattern (254 samples) and compared to control sera with negative cytoplasm (239 samples). All 493 samples were tested with a commercial synthetase profile dot-blot (D TEK - Alphadia-Alifax) including anti-Jo1, anti-PL7, anti-PL12, anti-EJ, anti-OJ, anti-KS, anti-ZO, anti-HA, anti-SRP, and anti-Ribosome P0. Retrospective clinical data was searched for positive patients. Dot-blot identified 18/254 (7.1%) positive sera in the samples with a cytoplasmic fluorescence pattern and 4/239 (1.7%) in the control group (χ2 = 8.4627; p = 0.003625). Blot intensity was more intense in samples with concordant cytoplasmic staining (cytoplasmic negative 27 ± 12.4; cytoplasmic positive 53.9 27 ± 27.7; p = 0.0027). In the positive samples, 8/18 had a highly compatible diagnosis (myositis, interstitial lung disease, arthritis), 7/18 an uncharacterized connective tissue disease, and 3 a diagnosis not associated with the presence of anti-synthetase antibodies. We evaluated the performance of a dot-blot assay for anti-cytoplasmic antibodies in a serologic cohort presenting a cytoplasmic speckled pattern found during routine ANA testing. This algorithm enabled the identification of a significant quota of patients with rare anti-synthetase antibodies and an incomplete or atypical clinical picture. Reflex testing strategies of speckled cytoplasmic patterns with multiplex assays containing cytoplasm-specific antigens, as opposed to standard ENA testing, may yield important data and for this reason should be implemented in routine ANA testing.

Bench to bedside review of myositis autoantibodies

Idiopathic inflammatory myopathies represent a heterogeneous group of autoimmune diseases with systemic involvement. Even though numerous specific autoantibodies have been recognized, they have not been included, with the only exception of anti-Jo-1, into the 2017 Classification Criteria, thus perpetuating a clinical-serologic gap. The lack of homogeneous grouping based on the antibody profile deeply impacts the diagnostic approach, therapeutic choices and prognostic stratification of these patients. This review is intended to highlight the comprehensive scenario regarding myositis-related autoantibodies, from the molecular characterization and biological significance to target antigens, from the detection tools, with a special focus on immunofluorescence patterns on HEp-2 cells, to their relative prevalence and ethnic diversity, from the clinical presentation to prognosis. If, on the one hand, a notable body of literature is present, on the other data are fragmented, retrospectively based and collected from small case series, so that they do not sufficiently support the decision-making process (i.e. therapeutic approach) into the clinics.

First report of anti-TIF1γ dermatomyositis in a patient with myelodysplastic syndrome

Inflammatory myopathies as para-neoplastic phenomena were first described by Sterz in 1916. Recently, myositis specific autoantibodies were described in cancer-associated myositis. Anti-transcription intermediary factor 1 gamma (anti-TIF1γ) antibodies have been found in both young adults affected by juvenile dermatomyositis and in elderly patients with cancer-associated myositis. In this regard, we report herein the first case of anti-TIF1γ dermatomyositis secondary to a myelodysplastic syndrome.

Omalizumab dampens type 2 inflammation in a group of long-term treated asthma patients and detaches IgE from FcεRI

Even if omalizumab is broadly used in the treatment of severe, allergic asthma, the immunological effects in long‐term treated patients have not been fully elucidated. To this aim, a cohort of 15 allergic asthmatic patients treated with omalizumab for at least three years was compared with 12 allergic asthma patients treated with standard therapy. Omalizumab treated asthmatic patients showed lower frequencies of circulating plasmacytoid DCs, and lower CD154 expression on CD4 T‐helper cells than the control group. Moreover, basophils and DCs from omalizumab‐treated patients had lower surface expression of IgE compared to the control group. In a longitudinal evaluation of two patients that started omalizumab treatment, we show that FcεRI free of IgE were evident on basophils just after four weeks of drug administration. Finally, in vitro experiments with basophils obtained from healthy donors confirm that omalizumab is able to detach IgE from high affinity IgE receptors.

Cutaneous leucocytoclastic vasculitis with anti-EJ autoantibodies: mere coincidence or a manifestation of antisynthetase syndrome?

T. Hashimoto, K. Teye, S. Numata, Y. Suga, T. Hamada and N. Ishii Kurume University Institute of Cutaneous Cell Biology, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan; Department of Dermatology and Allergology, Juntendo University Urayasu Hospital, Urayasu, Chiba, Japan; and Department of Dermatology, Kurume University School of Medicine, Kurume, Fukuoka, Japan E-mail: hashimot@med.kurume-u.ac.jp Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 18 June 2016