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Igg4-Related Chronic Sclerosing Dacryoadenitis

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Igg4-Related Chronic Sclerosing Dacryoadenitis There were no corneal lesions. The The patient had 1 recurrent epi- Correspondence: Dr Pollard, De- dilated fundus examination find- sode of bilateral iritis 4 months later partment of Ophthalmology, Chil- ings were normal. Blood studies were and now has been clear for 2 years. dren’s Healthcare of Atlanta at Scot- negative for antinuclear antibodies tish Rite Children’s Hospital, James and rheumatoid factors and showed Comment. Cogan syndrome mainly H. Hall Eye Center, 5445 Meridian a normal complete blood count and affects young adults but can appear Mark Rd, Ste 200, Atlanta, GA 30342 negative angiotensin-converting en- from ages 3 to 40 years. Slightly more ([email protected]). zyme levels. males are affected than females. The Financial Disclosure: None re- We diagnosed bilateral atypical etiology is unknown, but in approxi- ported. Cogan syndrome in the patient. mately 20% of cases, the onset is pre- Funding/Support:Thisstudywassup- The bilateral iritis resolved with ceded by an upper respiratory in- ported by a grant from the James H. cycloplegics and topical steroid fection. In 41% of cases, the eye is Hall Eye Center, Atlanta, Georgia. drops. The patient has been re- affected first; in 43%, the ear is af- 1. Haynes BF, Kaiser-Kupfer MI, Mason P, Fauci AS. ferred for a cochlear implant. He fected first; and in 16% of cases, both Cogan syndrome: studies in thirteen patients, had another episode of bilateral iri- organs are affected at the same time. long-term follow-up, and a review of the tis 3 months later, which also re- literature. Medicine (Baltimore). 1980;59(6): The interval between ocular and ear 426-441. solved with topical cycloplegic and involvement can be as short as 3 2. Cobo LM, Haynes BF. Early corneal findings in Cogan’s syndrome. Ophthalmology. 1984;91 steroid eye drops. months in the typical syndrome or Case 2. A 10-year-old white boy (8):903-907. as long as 11 years in the atypical 3. Orsoni JG, Zavota L, Pellistri I, Piazza F, Cimino had a history of bilateral red eyes for syndrome. Making the diagnosis of L. Cogan syndrome. Cornea. 2002;21(4):356- 1 month at initial examination. One 359. Cogan syndrome is important, not 4. Garcı´a Berrocal JR, Vargas JA, Vaquero M, Ramo´n year prior to this eye examination, only because vision can be lost, but y Cajal S, Ramı´rez-Camacho RA. Cogan’s syn- he had acutely lost all of his hear- drome: an oculo-audiovestibular disease. Post- ing and had undergone a cochlear also because 10% of cases are com- grad Med J. 1999;75(883):262-264. plicated with aortic insufficiency, 5. Vinceneux P. Cogan’s syndrome. Orphanet implant in his right ear. Visual acu- 4 Encyclopedia. 2003;134:1-7. ity was 20/30 OD and 20/20 OS. He which can be life threatening. Poly- had bilateral iritis with posterior syn- arthralgias or arthritis can also ac- echiae in the left eye. There were no company the disease. corneal lesions and the dilated fun- Neurologic findings, such as epi- dus examination findings were nor- lepsy or encephalitis, can also be IgG4-Related Chronic mal. Blood studies were performed seen. Almost 90% of patients have Sclerosing Dacryoadenitis and levels of rheumatoid factor, fluo- severe hearing loss or total bilateral rescent treponemal antibody absorp- deafness. When deafness is not com- Recent evidence suggests that tion, angiotensin-converting en- plete, high-dose corticosteroids can Mikulicz disease is distinct from zyme, and complete blood count lead to hearing improvement in 50% Sjo¨gren syndrome and is an IgG4- were all normal. The iritis resolved of cases, but if deafness is already related systemic disease.1 Herein quickly with topical dilating and cor- total, the corticosteroids do not we report 4 cases of Mikulicz dis- ticosteroid drops. Six months later, help.5 ease in which the serum IgG4 con- the patient had another episode of The atypical form of Cogan syn- centrations were elevated and infil- bilateral iritis without corneal in- drome can be an overlooked cause tration of IgG4-stained plasma flammation, which also resolved of uveitis in children; the disease had cells with sclerosing fibrosis was with topical drops. At the 2-year fol- been undiagnosed in our patients pathologically observed in the lac- low-up, there was no recurrence. until their initial visit to our office. rimal gland. Case 3. A 13-year-old white boy One patient had seen 9 physicians had a history of red eyes off and on before we made the association be- Report of Cases. Three women for the past 2 years, which were tween uveitis and sensorineural (aged 46, 47, and 64 years) and 1 treated with topical antibiotic drops. hearing loss. Many articles on pedi- man (aged 66 years) were referred He had lost all hearing acutely dur- atric uveitis do not even mention with swelling of the lacrimal gland ing a 2-week period 18 months pre- atypical Cogan syndrome as a cause region (Table). Every patient had viously. He had received a success- of uveitis. While most cases of uve- experienced a chronic episode (3 ful left cochlear implant. Visual itis will not involve sensorineural months to 5 years) of progressive acuity was 20/30 OU and bilateral iri- hearing loss, the small percentage eyelid swelling. The 64-year-old tis was present. There were no cor- that will be seen with this serious woman (patient 3) had a history of neal lesions and the dilated fundus complication warrants a recommen- surgical resection of a subcutane- examination findings were also nor- dation to evaluate the patient’s hear- ous mass in the upper eyelid, which mal. Blood tests showed that levels ing status when no etiology for the was pathologically diagnosed as lym- of fluorescent treponemal antibody uveitis is found. phoid hyperplasia at a different hos- absorption, rheumatoid factor, com- pital 2 years prior to the initial visit. plete blood cell count, and angio- Zane F. Pollard, MD Magnetic resonance imaging de- tensin-converting enzyme were all Marc Greenberg, MD picted well-circumscribed masses in- normal. The iritis resolved with topi- Alice Bashinsky, MD cluding bilateral lacrimal glands in cal cycloplegic and steroid drops. Mark Bordenca, MD the lacrimal fossa (Figure 1). In ev- (REPRINTED) ARCH OPHTHALMOL / VOL 125 (NO. 11), NOV 2007 WWW.ARCHOPHTHALMOL.COM 1575 ©2007 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 Table. Clinical Aspects of Patients With IgG4-Related Dacryoadenitis Patient No./ History of Salivary Gland Serum IgG Serum IgG4 IgG4:IgG Sex/Age, y Eyelid Swelling Swelling Concentration, mg/dLa Concentration, mg/dLa Ratio, % Medication 1/F/47 5 y Submandibular 2350 1000 43 Oral steroid 2/M/66 1 y Submandibular 1960 164 8 None 3/F/64 2 y Parotid submandibular 1820 486 27 Oral steroid 4/F/46 3 mo Submandibular 1350 209 15 Oral steroid a To convert milligrams per deciliter to grams per liter, multiply by 0.01. A B C D Figure 1. Magnetic resonance imaging before resection of the lacrimal gland. Bilateral masses including lacrimal glands are shown. A, Coronal T1-weighted image in case 1. B, Axial T1-weighted image in case 2. C, Coronal T1-weighted image with gadolinium enhancement in case 3. D, Axial T1-weighted image with gadolinium enhancement in case 4. ery patient, swelling of the salivary section of the mass including the lac- CD3) in all of the cases. Monoclonal- glands (submandibular or parotid) rimal gland. ity was also not evident in the infil- was also observed (Table). No pa- Lacrimal glands resected from 4 trating plasma cells, which were tients showed symptoms or ophthal- cases pathologically showed severe composed of ␬-positive cells and mic findings of keratoconjunctivitis lymphoplasmacytic infiltration with ␭-positive cells (not shown). Im- sicca. Laboratory data ruled out sys- lymphoid follicles and irregular fi- munostaining of IgG4 showed that temic diseases causative of so-called brosis (Figure 2). Inflammatory numerous IgG4-positive plasma cells Mikulicz syndrome, such as sarcoid- cells consisted of mature lympho- infiltrated the lacrimal glands in all osis, leukemia, and lymphoma. Con- cytes and plasma cells without any of the cases (Figure 2). IgG4- centrations of the serum IgG (refer- atypia. Glandular tissue was atro- positive plasma cells were com- ence range, 870-1700 mg/dL; to phied and associated with interaci- monly observed in inflammatory convert milligrams per deciliter to nar and intra-acinar sclerosing areas among lymphoid follicles grams per liter, multiply by 0.01) and inflammation. Hyalinized dense fi- (Figure 2D and H). IgG4 (reference range,Ͻ135 mg/ brosis was also observed in cases 1 Based on these findings, we di- dL) were obtained prior to treat- and 2 (Figure 2A and C). Immuno- agnosed these cases as chronic scle- ment (Table). In all of the patients, staining revealed that the lympho- rosing dacryoadenitis, consistent the serum IgG4 concentration and the cytes were polyclonal and com- with Mikulicz disease related to ratio of IgG4 to IgG were elevated. All posed of B cells (positive for CD20 IgG4. No patients manifested evi- of the patients underwent partial re- and CD79␣) and T cells (positive for dence for IgG4-related sclerosing (REPRINTED) ARCH OPHTHALMOL / VOL 125 (NO. 11), NOV 2007 WWW.ARCHOPHTHALMOL.COM 1576 ©2007 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 salivary glands. Beginning with the A B report by Morgan and Castleman2 in 1953, Mikulicz disease had been considered to be a subtype of pri- mary Sjo¨gren syndrome owing to their resemblance pathologically. However, later studies suggested that these 2 diseases were distinctly dif- ferent pathologically and clini- cally, ie, in Mikulicz disease, lacri- mal gland acinar cells maintained C D their function and were not pro- grammed for cell death.3 More re- cently, Mikulicz disease has been suggested to be a disorder involv- ing IgG4, the rarest subclass of IgG in healthy subjects.
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