MO YIN MOK, YI LO, PIK YIU LEUNG, and CHAK SING LAU

ABSTRACT.

Pregnancy outcome of patients with adult onset Still's disease (AOSD) has not been addressed. We report the maternal and fetal morbidity of 5 pregnancies from 3 Chinese patients with AOSD and review another 17 pregnancies from 14 patients reported in the English literature. Nine patients had their first manifestation in the 5th to 6th gestational month. Disease relapse in patients with known AOSD occurred most commonly in the post-partum period. Most did not respond satisfactorily to nonsteroidal antiinflammatory agents alone, but responded to administration of corticosteroids, especially in high doses. (J Rheumatol 2004;31:2307-9)

Key Indexing Terms:

EXACERBATION
FETAL OUTCOME
MATERNAL OUTCOME

M.Y. Mok, MBBS (HK), MRCP (UK), Rheumatologist; Y. Lo, Research Assistant; P.Y. Leung, Research Assistant; C.S. Lau, MBChB (Dundee), MD (Dundee), FRCP (UK), Professor of Medicine.

Address reprint requests to Dr. M.Y. Mok, Department of Medicine, Queen Mary Hospital, Pokfulam Road, Hong Kong.

Submitted December 11, 203; revision accepted May 26, 2004.

The effect of pregnancy on disease activity and maternal and fetal outcome in patients with adult onset Still's disease (AOSD) has not been well addressed. We describe pregnancies from 3 Chinese patients with AOSD and review the pregnancy outcome of patients satisfying the classification criteria for AOSD^1,2 (Table 1) reported in the English literature^3-12.

Table 1. Our cases and previous reported pregnancies in adult onset Still's disease.

CASE REPORTS

Case 1. A 30-year-old woman presented in April 1995 with low grade fever, weight loss, cervical lymphadenopathies, urticaria-like rashes, and polyarthritis affecting her fingers, wrists, and knees. Skin biopsy showed leukocytoclastic vasculitis. Blood tests revealed leukocytosis (24.6 ´ 10⁹/l), elevated erythrocyte sedimentation rate (ESR; 60 mm/h), and C-reactive protein (CRP) 13.5 mg/dl (normal < 0.6 mg/dl). There were also abnormal liver function tests [alkaline phosphatase (ALP) 167 U/l, ALT 38 U/l, AST 43 U/l] and hyperferritinemia (3985 ng/ml). Immune profiles including antinuclear antibodies and rheumatoid factor and septic examination were negative. AOSD was diagnosed and she was treated with methotrexate (MTX) 12.5 mg/wk, prednisolone 15 mg, and indomethacin 25 mg twice daily, with satisfactory response.

Relapse of polyarthritis and urticarial rash occurred at the 17th gestational week in October 1999. Blood tests showed leukocytosis (15.6 ´ 10⁹/l) and elevated ESR (30 mm/h) and CRP (4.7 mg/dl). Oral prednisolone 5 mg and hydroxychloroquine 200 mg daily were restarted. She had a premature delivery at the 33rd gestational week because of spontaneous rupture of the amniotic membrane. She remained well in the post-partum period.

Case 2. A 24-year-old woman was diagnosed with AOSD in October 1996, when she presented with high swinging fever, polyarthralgia, and urticarial and maculopapular rash at peaks of temperature. She was found to have leukocytosis (21.3 ´ 10⁹/l), hyperferritinemia (3990 ng/ml), elevated ESR (101 mm/h) and CRP (11 mg/dl), and negative septic investigations. She responded well to prednisolone 20 mg, hydroxychloroquine 200 mg, and indomethacin 50 mg 3 times daily, which were then stopped in late 1997.

She had one first-trimester miscarriage in March 1998 and a full-term normal delivery one year later. She had impaired glucose tolerance in the latter pregnancy. At the 21st gestational week of her third pregnancy in March 2003, she developed urticarial rash, polyarthralgia, and high fever. Blood tests showed leukocytosis (12.2 ´ 10⁹/l), abnormal liver function (ALP 96 U/l, ALT 35 U/l, AST 86 U/l), hyperferritinemia (3210 ng/ml), and elevated ESR (107 mm/h) and CRP (13 mg/dl). Septic investigation was negative. She was treated with prednisolone 60 mg daily with gradual tapering in dose. She delivered uneventfully at full-term with no relapse afterwards.

Case 3. A 22-year-old woman was diagnosed with angioimmunoblastic lymphoproliferative disease in February 1994, when she presented with high fever, polyarthralgia, cervical lymphadenopathies, splenomegaly, and maculopapular and urticaria-like rash. Three courses of chemotherapy were given, to no avail. Symptoms relapsed in January 1995 with leukocytosis (15.6 ´ 10⁹/l), abnormal liver function (ALP 229 U/l, ALT 41 U/l, AST 24 U/l), and elevated ESR (80 mm/h) and CRP (8 mg/dl). Exhaustive septic investigations and immune profiles were negative. Skin biopsy showed leukocytoclastic vasculitis. She was treated with prednisolone 60 mg, hydroxychloroquine 400 mg, and MTX 15 mg/week, with satisfactory response.

Her first pregnancy, in August 2001, was complicated by intrauterine growth restriction (IUGR). At 38 weeks' gestation, the baby was delivered by cesarean section after transient paroxysmal atrial tachycardia was detected. Anti-Ro/SSA antibodies were not present in the maternal serum by countercurrent electrophoresis. Immunoblotting did not show reactivity towards Ro52 and Ro60 peptides. She developed transient arthritis of the right wrist 2 months after delivery and was managed with naprosyn.

DISCUSSION

The role of hormonal factors was first postulated to influence disease susceptibility in AOSD when Bywaters¹³ noted a slight female predominance. Indeed, our literature review identified 10 patients with first manifestations and 7 exacerbations in 12 pregnancies in patients with known AOSD. Although only 3 pregnancies were reported to be uneventful, it is likely that good pregnancy outcomes from patients with established AOSD are under-reported.

First manifestations mostly occurred in the 5th to 6th gestational months (Table 1, Patients 5a, 6, 9, 11, and 12). Three patients manifested AOSD in the first trimester (Patients 10, 13, 15), one in the post-partum period (Patient 4a), and the timing of one was not mentioned (Patient 17). Exacerbations occurred despite inactive disease at conception, mostly in the post-partum period (Patients 4b, 14a, 16) from 3 days to 5 months after delivery or even following spontaneous abortion (Patient 14b). Two other exacerbations developed in the 4th to 5th gestational months (Patient 1, 2c). All episodes were classical acute systemic manifestations, except for one (Patient 4a) with an insidious onset of rash and arthritis. Elective termination of the pregnancy at the time of relapse did not result in ablation of disease activity (Patient 13). Transient articular symptoms of mild severity were also frequent complaints (Patients 3, 5a, 6, 7, 8).

Multiple exacerbations in the same pregnancy were not common (Patient 10). Rather, most symptoms resulted from incomplete treatment of an earlier exacerbation. Salicylates and nonsteroidal antiinflammatory drugs (NSAID) showed initial response, but there was a subsequent resurgence of symptoms within weeks (Patients 4b, 9, 10, 15, 16, 17). One patient with no systemic complaint (Patient 1) fared well with low dose prednisolone. Complete (Patients 6, 14a, 16) and partial (Patients 2c, 5a, 11) responses were achieved with moderate doses (≤ 0.5 mg/kg/day) of prednisolone. High dose prednisolone (1 mg/kg/day) was successful (Patients 2c, 4b, 9, 12, 13) and without adverse event. Pulse methylprednisolone, intravenous immunoglobulin (IVIG; Patient 10), and pulse cyclophosphamide (given after elective termination, Patient 13) were also reported to be efficacious. Disease modifying agents including hydroxychloroquine, gold salts, MTX, and azathioprine were used as maintenance therapy after delivery, with variable response.

Unfavorable pregnancy outcomes including spontaneous abortion (Patients 2a, 14b), prematurity (Patients 1, 7, 9, 11), and IUGR (Patients 3, 11) were occasionally observed. It is likely that prematurity and IUGR occur more commonly in pregnancies complicated by disease exacerbation. Maternal morbidities were not common. Impaired glucose tolerance (Patient 2b) and preeclampsia (Patient 10) were among those reported.

Patients with AOSD may experience exacerbation of disease in pregnancy. Corticosteroid therapy is generally safe and can achieve satisfactory response and perhaps better fetal outcome. Longterm data are needed for management of these patients.

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