Painless Scleritis Associated with Microscopic Polyarteritis:“Red Eye” as a Clue to Diagnose Systemic Diseases

Yosuke Sasaki, MD,1 Takayuki Rikitake, MD,1 Emiko Shindo, MD,1,2

Tomoko Okano, MD,3 Tadashi Matsumoto, MD,3

Natsuki Fujio, MD,2 Sei Muraoka, MD,2

Shinichi Kawai, MD, PhD,2 and Yoshihisa Urita, MD, PhD1

1 Department of General Medicine and Emergency Care, Toho University School of Medicine, Tokyo, Japan2 Division of Rheumatology, Toho University School of Medicine, Tokyo, Japan3 Department of Ophthalmology, Toho University School of Medicine, Tokyo, Japan

“Red eye” is the most common ocular manifestation seen by primary care physicians. Most cases are connected with

benign diseases, yet some may require emergent ophthalmologic intervention or herald a life-threatening systemic

disorder. Scleritis usually manifests as severe and painful red eye and is frequently associated with systemic vasculitis.

Herein, we report the case of an 81-year-old man with microscopic polyarteritis presenting with rapidly progressive

glomerulonephritis, diffuse alveolar hemorrhage, and bilateral painless scleritis. Our experience may remind clinicians

of the importance of “red eye” as a clue in the early diagnosis of systemic vasculitis, even in the absence of pain.

Keywords: episcleritis, microscopic polyarteritis, red eye, rapidly progressive glomerulonephritis, scleritis, vasculitis

Introduction

“Red eye” is the most common ocular manifestation

seen by primary care physicians. Most cases are

connected with benign diseases, yet some may require

emergent ophthalmologic intervention or herald a life-

threatening systemic disorder. Scleritis usually mani-

fests as severely painful red eye and is frequently

associated with systemic vasculitis.1 Herein, we report

a case of bilateral painless scleritis in association with

microscopic polyarteritis (MPA) presenting with rap-

idly progressive glomerulonephritis (RPGN) and

diffuse alveolar hemorrhage (DAH). Our experience

may remind clinicians of the importance of “red eye”

as a clue in the early diagnosis of systemic vasculitis,

even in the absence of pain.

Case Presentation

An 81-year-old man was admitted for the evaluation of

Corresponding author: Yosuke Sasaki, MD

Department of General Medicine and Emergency Care, Toho University School of Medicine, Omori Hospital, 6-11-1

Omori-Nishi, Ota-ku, Tokyo 143-8541, Japan

E-Mail: yousuke.sasaki@med.toho-u.ac.jp

Received for publication 17 May 2015 and accepted in revised form 3 September 2015

© 2016 Japan Primary Care Association

Journal of General and Family Medicine 2016, vol. 17, no. 4, p. 323–327.

Case Reports

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a low-grade fever following a three-month period of

anorexia with non-productive cough. During those

three months, his body weight had decreased from 67

to 60 kg. He had visited other hospitals and had been

prescribed 8 days of sitafloxacin 50mg twice a day and

then 10 days of clarithromycin 200mg twice a day,

which did not work. (No culture specimens were

obtained.) Two weeks prior to admission, the patient

developed a low-grade fever without chills. At that

time, he was only able to eat thin rice porridge. He had

also stopped drinking alcohol, although he was a

habitual drinker. Although he did not complain of any

ocular symptoms, his wife noticed that his eyes had

become reddish the day prior to admission. He denied

any neurological symptoms such as diplopia, dysarth-

ria, weakness, numbness, or difficulty walking.

The patient was treated for hypertension, hyperurice-

mia, and back pain with antihypertensives including an

angiotensin receptor blocker and a diuretic, allopurinol,

and a non-steroidal anti-inflammatory drug.

The patient lived independently with his wife. He had a

smoking history of 10 packs per year until 20 years

before. Prior to the onset of his anorexia, he had

consumed a glass of sake every night.

On physical examination, the patient appeared sick. His

blood pressure was 110/60mmHg, pulse rate was

regular at 86 beats per minute, respiration rate was 28

breaths per minute with 95% saturation in ambient air,

and body temperature was 36.1°C. Systematic exami-

nation revealed bilateral red eyes without eye wax, fine

late-inspiratory crackles in the bilateral lower lung

fields, and slight, slow pitting edema in both feet. A

detailed ophthalmologic examination revealed ciliary

injection, remarkable inflammation of the sclera, and

prominent dilation of the conjunctive vessels in both

eyes (Figure 1). Right and left eyesight, measured by

the Landolt ring chart, was 0.4 and 0.5, respectively.

Neurological examination was unremarkable. Labora-

tory examination (Table 1) was remarkable for leuko-

cytosis, normocytic anemia, elevated C-reactive protein

(CRP), and hypoalbuminemia with increased globulins.

Two months prior to admission, the patient’s renal

function was found to be normal at another hospital.

On admission, however, his renal function had

drastically deteriorated to as much as 10.1ml/min/

1.73m2 of the estimated glomerular filtration rate

(eGFR), with prominent microhematuria, proteinuria,

and various urine casts (Table 1). The computed

tomography (CT) scan of the chest revealed bilateral

ground-glass opacities. Bloody broncho-alveolar lav-

age fluid suggested DAH associated with pulmonary

renal syndrome.

Given the patient’s red eyes, we initially strongly

suspected MPA rather than Goodpasture syndrome and

immediately consulted with rheumatologists prior to

serological confirmation of the diagnosis, which was

Figure 1. Patient’s eyes on admissionNote: Ophthalmologic examination revealed ciliary injection, remark-able inflammation of the sclera, and dilation of the conjunctive vesselsin bilateral eyes (A, B). Conjunctive vessels were prominently dilated inthe right eye (C, Arrow).

Journal of General and Family Medicine 2016, vol. 17, no. 4

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Table 1. Laboratory data

Two months prior

to admissionOn admission

Two months

after admission

Blood examinations

Leukocyte (/mm3) 8,400 15,000 9,200

Neutrophil (%) 51.5 78.1 73.2

Lymphocyte (%) 37.5 11.5 22.6

Eosinophil (%) 3.1 5.9 0.1

Monocyte (%) 7.4 4.3 4.1

Basophil (%) 0.4 0.2 0

Hemoglobin (g/dL) 13 7.5 9.6

Hematocrit (%) 38.9 23 27.7

Platelet (©103/mm3) 263 319 150

Sodium (mEq/L) 142 133 No record

Potassium (mEq/L) 4.4 5.2 No record

Chloride (mEq/L) 103 103 No record

Glucose (mg/dL) No record 113 No record

BUN (mg/dL) 12.5 73 29.2

Creatinine (mg/dl) 0.93 4.72 1.78

eGFR (ml/min/1.73m2) 60 10.1 29.2

CRP (mg/dL) 3 16.8 0.1

Total protein (mg/dL) 7.9 7.9 5.6

Albumin (mg/dL) 3.7 1.8 No record

IgG (mg/dL) No record 2438 No record

IgA (mg/dL) No record 711 No record

IgM (mg/dL) No record 94 No record

Total bilirubin (g/dL) 0.5 0.4 0.5

AST (U/L) 31 39 24

ALT (U/L) 15 37 28

LDH (IU/L) 187 163 327

ALP (IU/L) 278 784 280

GGT (IU/L) 32 150 54

MPO-ANCA (U/mL) No record Ú300 19.6

PR3-ANCA (U/mL) No record 1 No record

Anti-nuclear antibody No record - No record

Urinalysis

Erythrocyte (/HPF) - Ú100 5–9

Leukocyte (/HPF) - 5–9 1–4

Protein (g/gCr) No record 0.9 No record

Hyaline cast - + +

Granular cast - + -

Epithelial cast - + -

Abbreviations: AST, aspartate aminotransferase; ALP, alkaline phosphatase; ALT, alanine amino-

transferase; BUN, blood urea nitrogen; CRP, C-reactive protein; eGFR, estimated glomerular filtration

rate; GGT, gamma-glutamyl transferase; HPF, high-power filed; IgA, immunoglobulin A; IgG,

immunoglobulin G; IgM, immunoglobulin M; MPO-ANCA, myeloperoxidase-anti-neutrophil cytoplas-

mic antibody; PR3-ANCA, proteinase 3-anti-neutrophil cytoplasmic antibody.

Painless Scleritis Associated with Microscopic Polyarteritis: “Red Eye” as a Clue to Diagnose Systemic Diseases

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obtained upon finding that the patient’s serum

myeloperoxidase anti-neutrophil cytoplasmic antibody

(MPO-ANCA) was elevated over 300U/mL. Anti-

glomerular basement membrane antibody was nega-

tive.

Soon after the confirmation of elevated MPO-ANCA,

rheumatologists immediately started a combination of

1mg/kg/day of oral prednisolone and monthly intra-

venous cyclophosphamide according to the protocol for

Japanese patients with MPO-ANCA-associated vascu-

litis.2 The fever, cough, and anorexia immediately

responded to the treatment. Two months after the

initiation of treatment, serum creatinine level had

improved to 1.78mg/dL. A follow-up chest CT scan

also showed improvement of bilateral opacities. The

red eye also responded to the systemic therapy for

MPA, as shown in Figure 2 (topical medication was

not required). Eyesight was measured two weeks after

admission and was unchanged.

Discussion

As noted above, red eye is usually benign but can

sometimes be a sign of a serious disorder that requires

immediate treatment. Emergent ophthalmologic con-

sultation is warranted in the following circumstances:

unilateral red eye with nausea and vomiting (which

suggests acute closed-angle glaucoma that reportedly

occurs in 12.2/100,000 patients in the Asian popula-

tion3); corneal infiltrate or opacity on fluorescein

staining; hypopyon; and severe ocular pain or visual

deficit in association with a red eye.4 Scleritis is an

uncommon ocular inflammatory disease of unknown

exact incidence. Scleritis is an important cause of red

eye because of the strong association with systemic

disorders and the potentially severe prognosis. Painful

red eye with severe, penetrating pain that radiates to the

forehead, brow, jaw, or sinuses is the typical manifes-

tation of scleritis.5 About half of all scleritis cases are

associated with underlying systemic disorders.1 The

most common of these is rheumatoid arthritis accom-

panied by vasculitis. The second most common is

granulomatosis with polyangitis (formerly Wegener’s

granulomatosis), in which, it is worth noting, scleritis

can present as the initial manifestation. Other systemic

diseases associated with scleritis include MPA, eosi-

nophilic granulomatosis with polyangitis, inflammatory

bowel disease, relapsing polychondritis, and other

vasculitides. Even tophaceous gout can cause scleritis

on occasion.6

Compared to episcleritis, scleritis requires more

intensive therapy and has a poorer prognosis. Scleritis

is generally subdivided into anterior scleritis (which

accounts for 90% of all scleritis) and posterior scleritis,

based on the portion of inflammation. These types

are respectively divided by the degree or range of

inflammation as follows: diffuse, nodular, or necrotiz-

ing.5 Diffuse anterior scleritis is the most common type

of scleritis, accounting for 50% of cases. Treatment

strategy differs among these subtypes; diffuse or

nodular anterior scleritis usually responds to mono-

therapy with non-steroidal anti-inflammatory drugs

(NSAIDs); necrotizing anterior scleritis or posterior

scleritis often requires aggressive therapy using a

combination of high-dose glucocorticoid and an

Figure 2. Patient’s eyes six weeks after admissionNote: Ciliary injection, inflammation of the sclera, and dilatation of theconjunctive vessels in bilateral eyes had completely improved withouttopical medications.

Journal of General and Family Medicine 2016, vol. 17, no. 4

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immunosuppressant such as cyclophosphamide.7

Two-thirds of patients with scleritis require intensive

immunosuppressive therapy.8 Despite aggressive ther-

apy, permanent visual disturbance occurs in approx-

imately 10% of patients with anterior diffuse scleritis,

25% with nodular scleritis, and 75 to 85% with

necrotizing scleritis or posterior scleritis.8,9

Episcleritis, a common and milder form of scleral

inflammation involving more superficial ocular tissue,

usually manifests as painless red eye. Episcleritis,

which accounts for 1.2% of ocular diseases,10 is

generally self-limited and is seldom associated with

systemic disorders.6

Given their differences with regard to ocular prognosis,

required treatments, and underlying disorders, correctly

distinguishing between scleritis and episcleritis is

important. The presence of subjective symptoms such

as ocular pain and visual impairment usually helps to

differentiate between scleritis and episcleritis. In some

atypical cases, however, the distinction may be difficult

when it must be made based on history and gross

physical examination alone. A detailed evaluation by

an experienced ophthalmologist is required in these

cases. In our case, the patient did not complain of any

ocular symptoms, although his wife and our clinical

staff noticed his red eyes. Accordingly, we consulted

with ophthalmologists to ensure a correct distinction

between scleritis and episcleritis, and concluded in

favor of scleritis based on the ophthalmologic findings

of remarkable inflammation and dilatation of the

vessels at the deep layer of the sclerae. Given the

patient’s age and ophthalmologic findings, the oph-

thalmologists judged that his eyesight was not acutely

injured. Painless scleritis has been reported in the

following situations: cases under the partial effect of

NSAIDs, posterior scleritis, and rare cases of sclero-

malacia perforans.5 Given that the present case is

anterior diffuse scleritis, our experience is rare and it

also suggests the unrecognized possibility of the

painless presentation of the most common subtype of

scleritis.

We hope that our experience will serve to remind

clinicians of the importance of considering red eye as a

possible manifestation of systemic vasculitis whenever

it appears in the company of other symptoms

suggesting vasculitis, such as nephritis, even in the

absence of pain. A red eye that is detectable at a glance

may help in the early diagnosis of vasculitis in primary

care settings.

Acknowledgements

We thank Dr. Hideki Nakamura (Nakamura Iin, Tokyo)

for his contribution to the report.

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