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Conjugal Giant Cell Arteritis

Chen, Meng BA; Gelman, Rachel BS; Al-Zubidi, Nagham MD; Kim, James D. MD; Lee, Andrew G. MD

Journal of Neuro-Ophthalmology: June 2013 - Volume 33 - Issue 2 - p 158–161
doi: 10.1097/WNO.0b013e319280d4c9
Clinical Observation
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Abstract: While the pathogenesis of giant cell arteritis (GCA) remains unclear, a number of factors may be contributory, including genetic, environmental, and immune. There have been few reports of GCA occurring in a conjugal pair, all originating from Northern Europe or the Northern United States. We document GCA occurring in a husband and wife from the southern Gulf Coast of the United States and discuss the implications of this, as well as the current understanding of the pathogenesis of GCA.

Baylor College of Medicine (MC, RG, AGL), Houston, Texas; Department of Ophthalmology (NA, AGL), The Methodist Hospital, Houston, Texas; Department of Ophthalmology (JDK, AGL), The University of Texas Medical Branch, Galveston, Texas; Department of Ophthalmology (AGL), The University of Texas Medical Branch, Galveston, Texas; Departments of Ophthalmology, Neurology, & Neurosurgery (AGL), Weill Cornell Medical College, New York, New York; Department of Ophthalmology (AGL), The University of Iowa Hospitals and Clinics, Iowa City, Iowa.

Address correspondence to Andrew G. Lee, MD, Department of Ophthalmology, The Methodist Hospital, Weill Cornell Medical College, Scurlock Tower, 6560 Fannin Street, Suite 450, Houston, TX 77030; E-mail: aglee@tmhs.org

Supported in part by an unrestricted grant to UTMB Galveston from Research to Prevent Blindness, Inc.

The authors report no conflicts of interest.

While the pathogenesis of giant cell arteritis (GCA) is unknown, immune, genetic, and environmental causes have been proposed. While rare, reports of GCA occurring in conjugal pairs (1–3) might provide information regarding immune and environmental factors. However, the subjects of these reports were either from Northern Europe or the northern United States of America (USA). In contrast, our patients (husband and wife) are from the southern USA, specifically the Gulf Coast region.

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REPORT OF CASES

A 76-year-old man was admitted to the hospital with the chief complaint of acute onset of temporary “vision loss in both eyes.” For 6 days, he had been experiencing crescendo episodes of bilateral transient visual loss, associated with new temporal and frontal headaches. He had been given a 6-day course of methylprednisolone 2 weeks previously for neck and back pain. Additional medical and social history is presented in Table 1. Visual acuity was 20/20 bilaterally. Examination of pupils, eye movements, visual fields, and the anterior and posterior segments was unremarkable.

TABLE 1

TABLE 1

The erythrocyte sedimentation rate (ESR) was 29 mm/hr, and a C-reactive protein (CRP) was 8.74 mg/dL (normal <1.52 mg/dL). Evaluation for thromboembolic disease, including cardiac and carotid catheter angiograms, was negative. Temporal artery biopsy showed chronic inflammation composed of lymphocytes and histiocytes at the internal elastic lamina, with areas of necrosis, consistent with treated GCA. The patient was started on prednisone 60 mg/d, and headaches and the episodes of transient visual loss resolved. A rheumatology consultant added methotrexate as a steroid-sparing agent. The patient reported that his wife also had biopsy-proven GCA, which had been diagnosed 10 years before his diagnosis.

His wife, a 66-year-old Caucasian woman, presented in 2002 with new-onset “temporal pain and double vision.” For 3 weeks, she experienced “bandlike” headaches, double vision, jaw claudication, and scalp tenderness. Medical and surgical histories are outlined in Table 1.

Her ophthalmologic examination was normal, but she had an elevated ESR of 94 mm/hr and a CRP of 17.7 mg/dL (normal 2.0 mg/dL). A temporal artery biopsy, showing foci of epithelioid cells and histiocytes, was consistent with the GCA. She was treated with 60 mg of prednisone daily, which was tapered over 7 months.

The spouses were not consanguineous, but both were of Scottish–English ancestry and had lived in the Gulf Coast for most of their lives. They met at college in Texas and resided primarily in Houston, Texas, but they also had lived in New York and New Jersey (6 years), England (5 years), and Australia (2 years). Both were fair skinned and reported spending approximately 2 months each year at a lake house, with increased sun exposure during the summer. Neither patient had any radiation or environmental toxin exposure. They did not own any pets during the wife's initial GCA presentation, although they have owned a dog for the past 8 years. There was no pertinent travel history, and neither patient had any history of tick bite, viral infection, or flulike illness at the time of presentation with GCA.

Regarding systemic disease, neither had ever tested positive for hepatitis B antigens. Although anticentromere and anti-Scl-70 antibodies were negative, the wife was diagnosed with scleroderma 22 years ago via skin biopsy. With progression of her symptoms, she was ultimately diagnosed with limited scleroderma and treated with plasmapheresis, leading to gradual improvement in her symptoms. Both the wife and her daughter have been diagnosed with fibromyalgia.

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DISCUSSION

While the cause of GCA is unknown, a number of reports suggest that genetic factors may be important. Review of the literature revealed 3 previously reported cases of GCA occurring in married couples (1–3). There have been 4 published cases of married couples with mixed presentations of polymyalgia rheumatica and GCA (4–7). These publications are summarized in Table 2.

TABLE 2

TABLE 2

There are 2 large studies of GCA occurrence in the southern USA, where our patients primarily live. In an 11-year retrospective review of GCA patients seen at the University of Texas Medical Branch, Gonzalez et al (8) found only 27 cases of GCA out of 101,239 patients (0.027%). Smith et al (9) found that from 1971 to 1980, in Shelby County, Tennessee, the average annual incidence of biopsy-confirmed GCA was 1.78 per 100,000 (0.00178%).

Both of our patients are of Scottish–English ancestry. Numerous studies have documented a higher occurrence of GCA in individuals of Northern European descent (10–12). In a 14-year retrospective study from Scotland, Jonasson et al (10) found the average annual incidence of biopsy-proven GCA to be 4.23 per 100,000 (0.00423%), which is approximately twice that found in Tennessee. There are other epidemiologic traits of GCA, including a higher frequency in women and occurring almost exclusively in persons older than 50 years (13).

Environmental factors may also play an etiologic role in GCA. Solar radiation may accelerate the fragmentation and degeneration of elastin fibers, a histologic feature of temporal artery biopsies. Both of our patients had an increased risk for sunlight exposure during frequent visits to their lake house. Additionally, the wife admitted to having a much greater exposure to sunlight than her husband did, and she developed GCA symptoms 10 years earlier. Both patients had long histories of smoking. In a multicenter, prospective study of 400 patients, Duhut et al. (14) found that in women, smoking was associated with a 6-fold increase in developing GCA, and heavy smoking (defined as >10-pack-years) was associated with a 13-fold increased risk. Interestingly, in men, while both smoking and heavy smoking cause slight elevations in GCA risk, this was not statistically significant. While the reason why smoking leads to greater susceptibility to GCA in women is unknown, Duhut et al postulated that smoking, which causes arterial wall damage, might lead to the generation of antigens that incite inflammatory/immunologic activity.

The immune system is heavily involved in GCA. The histologic hallmark of a positive temporal artery biopsy is infiltration of the tunica media by lymphocytes, histiocytes, and multinucleated giant cells, with disruption of the internal elastic lamina. Immunohistochemical studies have found that infiltrating lymphocytes are mostly CD4+ T-cells that secrete interferon-γ and interleuken-2, suggesting a Th1 response (15). Studies have also shown that in the adventitia, dendritic cells are activated (16). In the murine model, Weyand et al. have demonstrated that with antigen binding to toll-like receptors, dendritic cells differentiate to present antigen and activate CD4+ T-cells to secrete cytokines. This increased immune activity and inflammation result in intimal proliferation and arterial occlusion.

In searching for the antigen trigger for GCA, a variety of infectious etiologies have been proposed, including hepatitis B, rubella, herpes simplex, varicella zoster, measles, cytomegalovirus, Epstein–Barr virus, and other herpes viruses (3, 17). All remain unproven (18, 19). Katz et al (20) have found evidence of Burkholderia in blood and temporal artery biopsy specimens in patients with GCA using polymerase chain reaction, immunostaining, and bacterial culture. Other studies have focused on an infectious agent, based on cyclical GCA patterns or peak incidences of GCA after infectious epidemics. One large study of 10,818 patients in Denmark found 5 distinct peaks of GCA occurring in close association with 2 epidemics of Mycoplasma pneumoniae, 2 of parvovirus B19, and 1 of Chlamydia pneumoniae (21).

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