Eyes & Ears of Auto Immune

http://www.ufrgs.br/imunovet/molecular_immunology/pathohomotissueimmunity.html

Autoimmune diseases They are caused by autoimmune reactions and affect ~ 3-5% of the population with 2/3 of the patients being women. The site of attack is organ- or tissue-specific or more systemic : as the self-antigen(s) is usually expressed in more than one cell type, from an anatomical point of view autoimmune diseases should more properly be enclosed among the multi-organ failures (MOF). Anyway, due to common pathogenesis, I prefer to group them globally among the diseases affecting the immune system : a link to this page is provided in every page regarding involved organs. They can be classified as follows according to the main targeted organ(s) / apparatus(es) : sense organs eye autoimmune uveitis Aetiology : 5 < RR < 15 in individuals with HLA-B27 Pathogenesis : autoimmune anterior uveitis / iridocyclitis IgA nephropathy / Berger mesangial glomerulonephritis spondyloarthropathies (SpA) / spondyloarthritides-enthesoarthritides pauciarticular Still disease lens-induced uveitis / phacogenic uveitis phacoantigenic uveitis / phacoanaphylactic panophthalmitis occurs 2 weeks (required for sensitization) or months after lens capsular rupture (including surgery : expecially severe if patient had undergone extracapsular lens surgery) phacoanaphylaxis : hypersensitivity to the protein of the crystalline lens of the eye, induced by escape of material from the lens capsule phacotoxic uveitis is a low-grade phacoanaphylactic panophthalmitis phacolytic glaucoma : lens proteins leak through the capsule due to hypermature cataract => macrophages obstruct trabeculate, but no lymphocyte infiltration occurs Pathogenesis : autoimmune response to lens protein leaking through the capsule sympathetic ophthalmia (SO) / sympathetic uveitis / migratory ophthalmia Aetiology : 6-7 weeks after traumatic eye lesions intraocular surgery intraocular silicone oil ... in the contralateral eye causing antigen dissequestration : primary or exciting eye : the eye that is primarily injured and from which the influences start which involve the other eye in sympathetic ophthalmia secondary or sympathizing eye : the uninjured eye which becomes secondarily involved in sympathetic ophthalmia Pathogenesis : antibodies directed against retinal photoreceptors and pigment epithelium => bilateral progressive subretinal fibrosis and blindness with multifocal granulomatous chorioretinitis, preservation of the choriocapillaris (thanks to anti-inflammatory products secreted by the retinal pigment epithelium, including TGF-b and cystatin C / retinal pigment epithelial protective protein that is known to suppress the phagocyte generation of superoxide) and retina despite extensive inflammatory cell infiltration in the choroid Therapy : enucleation of the injured eye, otherwise blindness may occur. autoimmune posterior uveitis / choroiditis or panuveitis Aetiology : Behçet syndrome Heerfordt-Waldenström syndrome Wegener's granulomatosis rheumatoid arthritis diabetes mellitus nephropathies uveomeningitis / Vogt-Koyanagi-Harada (VKH) syndrome Aetiology : HLA-DR4, HLA-DRw53, and HLA-Bw54 Pathogenesis : Ab against the outer segments of photoreceptors and Muller cells Symptoms & signs : severe headache, vertigo, nausea and vomiting, very deep pain in the eyes => uveitis (first one eye and in a couple of weeks the other eye may become affected) with preservation of the choriocapillaris (thanks to anti-inflammatory products secreted by the retinal pigment epithelium, including TGF-b and cystatin C / retinal pigment epithelial protective protein that is known to suppress the phagocyte generation of superoxide) and retina (despite extensive inflammatory cell infiltration in the choroid) => retinal detachment => rapid vision loss, drowsiness, alopecia areata, autoimmune vitiligo, poliosis, hearing loss, facial nerve palsies, rigidity, walking (gait) disturbance Prognosis : after treatment sight and hearing usually return. However, there may be some permanent problems; hair loss with associated loss of color of the hair, eyelashes, and skin may remain. Lasting visual effects may include the development of secondary glaucoma and cataract. Experimental models : experimental autoimmune uveoretinitis (EAU) is a T cell mediated disease of the eye induced by immunization with S-arrestin / S antigen or interphotoreceptor retinoid-binding protein (IRBP). Mooren's ulcer Epidemiology : in elderly individuals Aetiology : trauma infections HHV-1 / HSV-1 HCV Salmonella spp. parasites Symptoms & signs : chronic serpiginous ulceration of cornea central to the most obvious crescent of epithelial defect and stromal melting developing in the corneal periphery, typically progressive centrally, centrifugally, and posteriorly, sometimes progressing to full corneal thickness and perforation. Therapy & prognosis : benign variant : unilateral form which often responds to intensive topical steroid therapy and/or conjunctival resection, malignant variant : bilateral form which progresses despite all attempted local treatments, and responds only to systemic immunosuppresssive chemotherapy. Web resources : Ocular immunology at Massachusetts Eye and Ear Infirmary ear Meniere's or Ménière disease / autoimmune inner ear disease (AIED) / labyrinthine vertigo / recurrent aural vertigo Epidemiology : prevalence 0.4% in USA, onset after age 50. Ménière’s disease, first described in 1861, is idiopathic endolymphatic hydropsref (excess fluid in the inner ear, first revealed through temporal bone studies in 1938), causing deafness, tinnitus, and vertigo. The median time of onset is the fourth decade; Ménière’s disease is rare in childrenref1, ref2, ref2. It is also probably underdiagnosed. Children who complain of dizziness tend to be overlookedref, perhaps partly because they have difficulty describing it, and because vaguely defined “dizziness” has many possible causes. Therefore, children with Ménière’s disease often present with vomiting—which can easily be misdiagnosed as cyclic vomiting or migraine (including abdominal migraine). Hearing loss sometimes develops after onset of the diseaseref1, ref2. Audiometry can be useful in identifying the cause of unexplained vomiting or “dizziness”; regrettably, it is not always widely availableref. Pathogenesis : autoantibodies against COCH5B2, stress and emotional disturbancesref seem to contribute to attacks. Elevation of plasma vasopressin levels (probably as a result of stress) may present as a matter of consequence, but susceptibility of the V2R-overexpressed and cAMP-hypersensitized inner ear to plasma vasopressin elevation might be essential as the basis of this diseaseref Symptoms & signs : unilateral (90%) or bilateral (10%) episodic turning or whirling vertigo (absent if endolymphatic distention is limited to the cochlea) that may lead to nausea and vomiting, and even prostration, tinnitus (varying from a whistle to a roar), and deafness. The onset of symptoms is insidious, usually with a sensation of dullness or fullness in the ear, and an initial fluctuation in hearing of 10 to 30 dB, usually in the low tones. The hearing improves somewhat between attacks, but it continues to deteriorate as time goes on. There may be increased sensitivity to sound, or music may sound distorted. Any head movement aggravates the condition, with the vertigo lasting several hours. Some patients can have fleeting attacks lasting several minutes, and still others have attacks lasting a week or longer and may take months to regain normal equilibrium. Laboratory examinations : spontaneous nystagmus, usually rotary and often direction-changing, and a direction-fixed, positional nystagmus are the most common findings no nystagmus at rest; reactive nystagmus elicted from caloric reflex testing (with warm and cold water) in the contralateral ear. Aside from the hearing loss, Meniere's patients frequently have recruitment and diplacusis, low threshold discomfort, and low discrimination scores. Tone decay and a type II Bekesy are present. Pure-tone audiometry showed mild sensorineural hearing loss in the affected ear glycerin test, where a patient ingests 1.5 gm/kg body weight of glycerol mixed with equal parts of normal saline and a few drops of lemon juice. Audiograms are taken immediately and at 1, 2, and 3 hr after ingestion. A positive test is said to be an improvement in hearing of 15 dB in any one frequency from 250 to 4000 Hz or 12% improvement in the discriminating score. Differential diagnosis : Ménière-like syndromes Therapyref : neutral-ash, sodium-free diet, supplemented with diuretics (isosorbide, an osmotic diuretic), regimen of bed rest, no smoking, plus inhalation of 5% CO2 + 95% O2 for 30' q.i.d. and 2.75 mg of histamine diphosphate in 250 cc of lactated Ringer's solution I.V. b.i.d. Other drugs, given individually, that are reported to be effective for an acute attack are 1/150 grain atropine I.V., diazepam 10 mgm I.V., and fentanyl citrate + droperidol, which must be administered in the hospital or by an anesthesiologist. Vasodilators are usually ineffective in Meniere's, as are the antivertiginous drugs. office-based intratympanic inner ear steroid perfusion (ITPs) treatmentref Meniett pulse generatorref vestibular ablation chemical intratympanic high-concentration gentamycinref1, ref2 destructive labyrinthotomy endolymphatic sac to mastoid shuntsref provided improvement in major spells of vertigo in 77% of patients at 24 months after surgery. Revision surgery provided improvement in 65% of cases. Results of revision surgery were better in those patients who developed recurrent symptoms more than 24 months after their original procedure compared with those of patients who failed treatment earlier triple semicircular canal occlusion (TSCO)ref low-level laser therapy (LLLT)ref Web resources : Autoimmune inner ear disease by Timothy C.Hain ulcerative colitis relapsing polychondritis systemic lupus erythematosus polyarteritis nodosa Cogan’s syndrome Wegener’s granulomatosis