Not always true Dr Aisling Loy GUM SPR

Not always true… Dr Aisling Loy GUM SPR

Presenting history • DY 39 year old female from Israel living in Ireland 20 yrs • Referred by GP Oct 12 with several day hx of painful mouth and genital ulcers • Hx of falling downstairs 1 week prior. • Multiple bruises from fall

History • Past Medical Hx of Hidradenitis suppurativa, recurrent oral apthous ulcers x 8 years • Fam Hx-

Hx Lives with partner 25 pkyr Hx Occasional C 2 H 5 OH No children • Father has Familial Mediterranean Fever and Ankylosing spondylitis • Aunt Behcets

Examination • • Normal vitals CVS/GIT/Resp/Neuro NAD Mouth- multiple ulcers, white coating GU- 2 x 2 cm ulcers on left labia majora. Indurated and tender.

Laboratory • • • WCC 29. 3 Neut 25 Hb 15. 2 Plat 315 CRP 248 ESR 22 U/E NAD CXR NAD ECG NSR

Management plan • • Ulcer swabs taken IV Augmentin/ prophylactic clexane Tramadol/Tylex ANA/ANCA sent HIV serology HSV serology GUM and Derm consults

Progress • Reviewed by GUMTemp spike 38. 5 and continued to spike for next 2 days. • Blood cultures taken • STI screen • ? Behcets • Opthalmology review requested • Skin Bx taken from Vulva

Treatment • • Commenced Dermovate Topical Beclamethasone Oral Valtrex ? HSV Fluconazole

Skin Bx result • Skin Bx- dermal inflammation comprising of lymphocytes, histocytes and polymorphs. There are ectatic vascular spaces.

Results • • Xray of SI joints NAD ANA neg ANCA neg CRP continued to improve STI screen neg HSV culture neg Hep B/C EBV Neg

Progress • • Discharged home after 2 weeks Completed 7 days of IV/PO Augmentin CRP reduced Poor initial response to topical dermovate Changed to Colchicine 1 mg BD for 2 weeks Followed up in OPD Acute inflammation of the apocrine glands Special stains for Herpes virus, fugi, Mycobacteria and bacteris are negative.

2 weeks later in OPD • Sig response to colchicine, not completely healed • Returned to Isreal reviewed by Behcet specialist • Continued on 1. 5 mgs OD • For Exacerbation prednisolone 20 mgs • HLAB 51 neg

Dx with Behcets • What is Behcets? • Why did she develop Behcets now? • Is there a link to her family hx and her own medical Hx? • What will the future hold?

Hx of Behcets • Hulusi Behcet (18891948 ) • Turkish Physician • In 1937, described the classic trisymptom complex of hypopyon, iritis, and orogenital aphthosis

2500 yrs ago • Hippocrates of Kos (460 -377 BC) • Endemic disease in Asia Minor characterised by “aphthous ulcerations, defluxions about the genital parts, watery ophthalmies of a chronic character. . . which destroyed the sight of many persons, large herpetic lesions. ”

Spectrum of organ involvement in Behçet’s disease. Verity D H et al. Br J Ophthalmol 2003; 87: 1175 -1183 © 2003 by BMJ Publishing Group Ltd.

Laboratory • Mild anemia and leukocytosis • The ESR, C-reactive protein may be raised. • Serum immunoglobulin levels, especially immunoglobulin A, may be elevated. • Circulating immune complexes.

• Rheumatoid factor and antinuclear antibodies are absent.

Cutaneous manifestations

Joint manifestations • 50% develop signs or symptoms of synovitis, arthritis, and/or arthralgia. • The most frequent minor feature in childhoodonset BD. • Multiple-joint involvement is common.

Vascular involvement • This occurs in 7 -29% of patients, mostly men. • The 4 types of vascular lesions arterial occlusions, venous occlusions, aneurysms, and varices. • Arterial complications account for 7% of cases.

Gastrointestinal involvement • • 10% of patients with BD. Anorexia, vomiting, dyspepsia, diarrhoea, abdominal distention, abdominal pain

Neurologic manifestations • Varies from 3. 2 -49%. (rare) • Neurologic involvement may present in various combinations. • Most serious complications, high fatality rate. • Occur within 5 years of disease onset • Severe headache is the most frequent.

Behçet’s disease is associated with multiple hereditory and environmental risk factors. Verity D H et al. Br J Ophthalmol 2003; 87: 1175 -1183 © 2003 by BMJ Publishing Group Ltd.

Genetics • HLA-B 51 • Associated with Factor V Leiden deficiency • Displays genetic anticipation • More common in Isreal Arabs than Jews.

Immunological Abnormalities • Neutrophil infiltration, endothelial cell swelling, fibrinoid necrosis. • Increased levels of neutrophil priming cytokines, TNF, IL 1 B, IL 8, myeloperoxidase levels • ? genetic v primining agent v both

? Infective aetiology • Silk road promoted the spread of infection eg the black death, the plague of Athens. Behcet suspected an infectious aetiology • Monocytes show hypersensitivity to Streptococccal sanguis antigen • Higher levels of HSV 1 antibodies

Behçet’s disease. Verity D H et al. Br J Ophthalmol 2003; 87: 1175 -1183 © 2003 by BMJ Publishing Group Ltd.

Link to Familial Mediterranean Fever • Gene ass’d with FMF (MEFV) • 4 mutations ass’d with Behcets • Gene codes for pyrin thought to regulate neutrophils • Similar ethnic distribution and effect on neutrophils • Thought these two are linked to same gene. • Thought to be a link with hidradenitis suppurativa

Conventional Treatment

SYSTEMIC RX Azathiopine Interferon alpha Cyclophosphamide Cyclosporin Infliximab Etanercept Adalimumab Rituximab Anticoagulants

Novel Treatments • • • Probiotic yoghurt Topical Tacrolimus Sublingual interferon alpha Zinc sulphate mouth wash Nigella sativa oil

Why now? • Genetically primed plus a stress on the body starting a cytokine/neutrophilic/lymphocytic/ hyper response leading to a pathological systemic vasculitic phenonomen

Summary • Multisystem • Complex aeitology, both genetic and environmental • Varying prognosis • No specific diagnostic test • Treated with different methods of immune modulation.