0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Research Letters |

Granulomatous Choroiditis in Wegener Granulomatosis FREE

Alan D. Proia, MD, PhD
[+] Author Affiliations

Author Affiliation: Department of Pathology, Duke University Medical Center, Durham, North Carolina.


Arch Ophthalmol. 2011;129(4):512-526. doi:10.1001/archophthalmol.2011.62.
Text Size: A A A
Published online

Wegener granulomatosis (WG) is characterized classically as the triad of necrotizing granulomatous lesions of the upper and lower respiratory tract, focal segmental glomerulonephritis, and necrotizing vasculitis of small arteries and veins.1 Ophthalmological disease is the manifesting feature of WG in 8% to 16% of patients1 but develops in an estimated 50% to 60% of patients.2 Orbital disease is the most common ophthalmological manifestation of WG, uveal involvement is uncommon,2 and granulomatous sclerouveitis is rare.35 I describe the first histological documentation, to my knowledge, of granulomatous choroiditis in WG in the absence of scleritis.

A 71-year-old man developed protracted nausea, a 6.75-kg weight loss, acute renal failure, and pulmonary hemorrhage. He had positive results on a perinuclear antineutrophil cytoplasmic autoantibody assay and an antimyeloperoxidase enzyme-linked immunosorbent assay (level = 130.8 U; positive >20.0 U) and negative results on an antiproteinase 3 enzyme-linked immunosorbent assay (level = 3.9 U; positive >20.0 U). Although he did not have the typical pattern of antineutrophil cytoplasmic antibodies with cytoplasmic staining, his findings were considered most compatible with WG. His renal failure did not resolve with hemodialysis, high-dose methylprednisolone sodium succinate, cyclophosphamide, and plasmapheresis. He had progressively decreasing strength, mental status, and ability to tolerate tube feeding and died approximately 5 months after his initial symptom of nausea developed. A complete autopsy confirmed the diagnosis of WG with necrotizing granulomatous and fibrinous vasculitis with neutrophils and karyorrhectic debris involving the kidneys, testes, appendix, liver, spleen, lungs, pancreas, lymph nodes, small and large intestines, trachea, aorta, pericardium, myocardium, and both orbits (listed in order of decreasing histological severity).

The posterior choroid of both eyes had many foci of granulomatous inflammation similar to those in other organs with mostly epithelioid cells accompanied by lymphocytes and a few multinucleated giant cells (Figure 1). In multiple areas, the choriocapillaris was infiltrated by inflammatory cells and the capillaries were stenotic or occluded by inflammatory cells (Figure 2). Rare minute foci of fibrinoid necrosis with occasional neutrophils and karyorrhectic debris were in the choroid just beneath the choriocapillaris (Figure 2). The choroidal vessels were surrounded by the dense inflammatory infiltrate, but only a rare artery appeared to have its wall infiltrated by lymphocytes without necrosis. Degeneration of the neurosensory retina and scleral inflammation were not seen. Microorganisms were not detected using histochemical stains.

Place holder to copy figure label and caption
Figure 1.

The posterior choroid of both eyes had many foci of granulomatous inflammation. A confluent area of granulomatous inflammation is to the left in the photomicrograph, while 2 smaller granulomas (asterisks) are to the right (hematoxylin-eosin). Scale bar indicates 100 μm.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

The foci of granulomatous inflammation in the choroid contained mostly epithelioid cells accompanied by lymphocytes. The choriocapillaris (asterisk) is occluded by inflammatory cells. A small focus of fibrinoid necrosis has occasional neutrophils and karyorrhectic debris (arrows) (hematoxylin-eosin). Scale bar indicates 25 μm.

Graphic Jump Location

Choroidal involvement in WG may manifest clinically as uveitis, choroidal folds, retinal epithelial pigmentary changes, choroidal arterial occlusion, or choriocapillaritis.1,2 Only 1 histological description of isolated choroidal involvement by WG exists, to my knowledge.6 The patient described by Cutler and Blatt6 died 43 months after the onset of his illness, and there was a light but diffuse infiltrate of lymphocytes throughout the choroid; marked sclerosis of choroidal blood vessels with medial fibrosis and plump, prominent endothelial cells; prominent edema and fibrosis; areas of necrosis and hyperplasia of the retinal pigment epithelium; and degeneration of the overlying sensory retina.

In my patient, both eyes had many foci of granulomatous inflammation in the posterior choroid, rare minute foci of fibrinous necrosis in the choroid just beneath the choriocapillaris, and areas where the choriocapillaris was infiltrated by inflammatory cells. The inflammatory infiltrate in my patient resembled the granulomatous sclerouveitis reported in WG,35 which contains a mixture of T and B lymphocytes, macrophages, and enhanced expression of adhesion molecules and ligands.5 I postulate that the difference in the histological appearance of the choroid in my patient's eyes and that reported by Cutler and Blatt is due to the shorter duration of the WG in my patient and its stage of activity at the time of death. However, I cannot exclude the possibility that the difference reflects underlying variation in choroidal manifestation of WG.

Correspondence: Dr Proia, Department of Pathology, Duke University Medical Center, DUMC 3712, Durham, NC 27710 (proia001@mc.duke.edu).

Financial Disclosure: None reported.

Harman  LEMargo  CE Wegener's granulomatosis. Surv Ophthalmol 1998;42 (5) 458- 480
PubMed Link to Article
Pakrou  NSelva  DLeibovitch  I Wegener's granulomatosis: ophthalmic manifestations and management. Semin Arthritis Rheum 2006;35 (5) 284- 292
PubMed Link to Article
Brubaker  RFont  RLShepherd  EM Granulomatous sclerouveitis: regression of ocular lesions with cyclophosphamide and prednisone. Arch Ophthalmol 1971;86 (5) 517- 524
PubMed Link to Article
Janknecht  PMittelviefhaus  HLöffler  KU Sclerochoroidal granuloma in Wegener's granulomatosis simulating a uveal melanoma. Retina 1995;15 (2) 150- 153
PubMed Link to Article
Levy-Clarke  GDing  XGangaputra  S  et al.  Recalcitrant granulomatous sclerouveitis in a patient with granulomatous ANCA-associated vasculitis. Ocul Immunol Inflamm 2009;17 (2) 83- 87
PubMed Link to Article
Cutler  WMBlatt  IM The ocular manifestations of lethal midline granuloma (Wegener's granulomatosis). Am J Ophthalmol 1956;42 (1) 21- 35
PubMed

Figures

Place holder to copy figure label and caption
Figure 2.

The foci of granulomatous inflammation in the choroid contained mostly epithelioid cells accompanied by lymphocytes. The choriocapillaris (asterisk) is occluded by inflammatory cells. A small focus of fibrinoid necrosis has occasional neutrophils and karyorrhectic debris (arrows) (hematoxylin-eosin). Scale bar indicates 25 μm.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 1.

The posterior choroid of both eyes had many foci of granulomatous inflammation. A confluent area of granulomatous inflammation is to the left in the photomicrograph, while 2 smaller granulomas (asterisks) are to the right (hematoxylin-eosin). Scale bar indicates 100 μm.

Graphic Jump Location

Tables

References

Harman  LEMargo  CE Wegener's granulomatosis. Surv Ophthalmol 1998;42 (5) 458- 480
PubMed Link to Article
Pakrou  NSelva  DLeibovitch  I Wegener's granulomatosis: ophthalmic manifestations and management. Semin Arthritis Rheum 2006;35 (5) 284- 292
PubMed Link to Article
Brubaker  RFont  RLShepherd  EM Granulomatous sclerouveitis: regression of ocular lesions with cyclophosphamide and prednisone. Arch Ophthalmol 1971;86 (5) 517- 524
PubMed Link to Article
Janknecht  PMittelviefhaus  HLöffler  KU Sclerochoroidal granuloma in Wegener's granulomatosis simulating a uveal melanoma. Retina 1995;15 (2) 150- 153
PubMed Link to Article
Levy-Clarke  GDing  XGangaputra  S  et al.  Recalcitrant granulomatous sclerouveitis in a patient with granulomatous ANCA-associated vasculitis. Ocul Immunol Inflamm 2009;17 (2) 83- 87
PubMed Link to Article
Cutler  WMBlatt  IM The ocular manifestations of lethal midline granuloma (Wegener's granulomatosis). Am J Ophthalmol 1956;42 (1) 21- 35
PubMed

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

732 Views
14 Citations
×

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
Jobs