Respiratory Medicine CME
Volume 2, Issue 2 , Pages 70-72, 2009

Adult-onset Still's disease and pulmonary arterial hypertension

  • Maria Eduarda Menezes de Siqueira

      Affiliations

    • Department of Internal Medicine, Hospital Santa Isabel, Floriano Peixoto 300 89010-906 Blumenau-SC, Brazil
    • Corresponding Author InformationCorresponding author. Tel.: +55 (47) 33228487/91876600; fax: +55 (47) 33228487.
    • ,
  • Roger Pirath Rodrigues

      Affiliations

    • Department of Pneumology, Universidade Regional de Blumenau and Hospital Santa Isabel, Brazil
    • ,
  • Adrian Paulo Morales Kormann

      Affiliations

    • Department of Interventional Cardiology, Hospital Santa Isabel, Brazil

Received 28 July 2008; accepted 15 October 2008.

Article Outline

Summary 

Pulmonary arterial hypertension (PAH) occurs with several rheumatologic diseases, however, it is rarely reported with Adult-onset Still's disease (AOSD). Pulmonary arterial hypertension is a major cause of morbidity and mortality. We describe a patient with AOSD who developed the characteristic clinical and hemodynamic findings of idiopathic PAH with persistent hypoxemia. A remission was obtained with immunosuppressive treatment without addition of prostaglandins, endothelin antagonists or phosphodiesterase 5 inhibitors.

Keywords: Adult-onset Still's disease, Pulmonary arterial hypertension, Acute respiratory failure, Autoimmune rheumatic diseases

 

Back to Article Outline

Introduction 

Adult-onset Still's disease (AOSD) is a rare adult variant of systemic juvenile rheumatoid arthritis. AOSD is characterized by an acute febrile syndrome that affects multiple organs. The diagnosis is one of clinical suspicion, requiring the exclusion of infection, malignancy, and systemic disease.1 The condition is usually characterized by spiking fever, maculopapular rash, sore throat, polyarthralgia, arthritis, lymphadenopathy, hepatosplenomegaly and serositis. AOSD has no specific laboratory criteria, but is common to find leukocytosis, thrombocytosis and elevated acute-phase reactants in AOSD patients.2 Cardiopulmonary manifestations include pneumonitis, pleuritis, and pericarditis with effusions, which rarely progress to acute respiratory distress, pericardial tamponade and myocarditis. Pleuritis and pericarditis are quite common when detected as a result of pleuritic chest pain, an auscultatory rub, or the demonstration of pleural or pericardial fluid by abnormal chest radiographs, ultrasonography or echocardiogram.3 Pulmonary arterial hypertension (PAH) is a major cause of morbidity and mortality in connective tissue diseases. The pathogenesis of PAH secondary to connective tissue diseases is unknown. Immune and inflammatory mechanisms could play a role in PAH pathogenesis in these patients.4 Pulmonary arterial hypertension is rarely described with AOSD and, to our knowledge, just three cases have been reported.4, 5, 6 Treatment of AOSD is empirical in the absence of randomized trials because of the rarity of the disease. Non-steroidal anti-inflammatory drugs are rarely sufficient, and almost all AOSD patients require corticosteroids.3 Here, we describe a patient with AOSD who developed the characteristic clinical and hemodynamic findings of idiopathic PAH with persistent hypoxemia. The patient had an excellent response after treatment for AOSD, with remission of PAH.

Back to Article Outline

Case report 

An 18-year-old man was brought to us with a history of high spiking fever, weight loss, polyarthralgia, and maculopapular rash, where all the symptoms had been present for 20 days. He was previously healthy. He denied tobacco, alcohol, or illegitimate drug or weight loss drug use. The patient was being treated for community-acquired pneumonia with levofloxacin. On examination, he was febrile (39°C), had a pulse of 100beats/min, a respiration rate of 30min−1, and a blood pressure of 128/87mmHg. The chest was clear on auscultation. There was no synovitis, hepatosplenomegaly, sclerodactyly, lymphadenopathy, calcinosis or skin tightness, and his body mass index was 35. Laboratory investigation showed a total leukocyte count of 32,600p/mm3, a hemoglobin level of 10.2g%, a platelet count of 200,000p/mm3, an ESR of 58mm/1sth, a ferritin level of 2000ng/ml, a prothrombin time of 12s, an INR of 1, an aspartate aminotransferase level of 85IU/L, an alanine aminotransferase level of 64IU/L, and a lactate dehydrogenase level of 1081IU/L. Serology tests for hepatitis B and C, Epstein–Barr virus and human immunodeficiency virus were negative. The results of urinalysis, stool analysis and blood culture were normal. Rheumatoid factors, ASO, antinuclear antibody, and antiphospholipid antibody were also negative. An abdominal ultrasound was normal. After the exclusion of infection, malignancy, and systemic disease, the diagnosis of AOSD was suggested. After four days, the patient began complaining of pleuritic chest pain and progressive exertional dyspnea. The oxygen saturation with supplementary oxygen was 90%. The arterial blood gas analysis revealed hypoxemia (PO2 65mmHg) and hyperventilation (PCO2 28mmHg). A ventilation perfusion scintigraphy and computed tomogram of the chest were negative for pulmonary embolism. There was no evidence of pleural or parenchymal involvement of the lung, pulmonary vasculitis, or immune deposition in the pulmonary vasculature. Spirometry suggested mild restrictive lung disease probably due to obesity [FVC 74% (4.36L), FEV1 77% (3.78L), VEF1/FVC 103% (0.84L)]. The diffusing capacity for carbon monoxide was 62% (7.52mM/min/KPa) with low reduction. A transesophageal Doppler echocardiogram showed no vegetation and intact interatrial and interventricular septa. A right heart catheterization confirmed the presence of pulmonary hypertension, with a main pulmonary artery pressure of 58/10mmHg, but normal capillary wedge pressure of 9mmHg. The patient was classified as NYHA class III. He was treated with indomethacin, prednisone (60mg/day) and methotrexate (20mg/week). The heart catheterization was repeated after 6 months of treatment; the main pulmonary artery pressure was 35/06mmHg with a capillary wedge pressure of 6mmHg. The patient had no more symptoms. A regression of the PAH was obtained with immunosuppressive treatment without addition of prostaglandins, endothelin antagonists or phosphodiesterase 5 inhibitors.

Back to Article Outline

Discussion 

We have reported a case of an 18-year-old man who was diagnosed with AOSD and presented with PAH. The patient's pulmonary pressure was increased at rest (58/10mmHg). His normal pulmonary artery wedge pressure excluded significant left ventricular dysfunction as a cause for the PAH. The echocardiogram showed no valvular or congenital heart disease. In the history, the patient had denied sleep-related breathing problems or the use of anorexigens. Viral serologies and anti-HIV were negative. Liver cirrhosis and portal hypertension could be excluded by the results of the abdominal ultrasound scan. Ventilation perfusion scintigraphy revealed no central chronic pulmonary thromboemboli and there were no defects apparent on the perfusion lung scan. The lung parenchyma appeared normal on chest CT, excluding interstitial lung disease as a cause of the patient's PAH. In patients with connective tissue diseases, PAH may occur in association with interstitial fibrosis or as a result of direct proliferative vascular involvement in the absence of significant parenchymal disease or chronic hypoxia. The pathophysiology is unknown, but the clinical course and pathological findings are similar to primary pulmonary hypertension. Several authors have hypothesized that immunological disturbances promote the development of pulmonary arteriopathy in these patients. A pulmonary vasospasm, the so-called pulmonary Raynaud's phenomenon, could hypothetically play a role. The presence of antinuclear antibodies, rheumatoid factor, immunoglobulin-G, and complement fraction deposits in the walls of pulmonary vessels suggests a role for an immunological mechanism.7 Scleroderma represents the main connective tissue disease associated with PAH. Pulmonary hypertension also occurs in other autoimmune rheumatic disease like systemic lupus erythematosus, mixed connective tissue disease, dermatomyositis, rheumatoid arthritis, Sjögren's syndrome and antiphospholipid antibody syndrome.8, 9 The prognosis is very poor, and no curative treatment is available. In the absence of major trials on pulmonary hypertension secondary to connective tissue diseases, treatment should be conducted in the same way as for idiopathic pulmonary hypertension.10 The difference is that immunosuppressive therapy may be effective in only a few patients with pulmonary hypertension secondary to connective tissue diseases. In the literature, there are several reports describing regression of PAH during treatment with corticosteroids associated with immunosuppressants in patients with rheumatologic diseases. Prospective studies are needed to confirm this clinical observation.7, 11 Our patient developed PAH with no apparent parenchymal involvement; this was probably an inflammatory pulmonary vasculopathy related to AOSD. After treatment with glucocorticosteroids and indomethacin for AOSD, the patient showed improvement in the hemodynamic parameters on right heart catheterization and NYHA functional class. We describe, to our knowledge, the fourth case of pulmonary hypertension complicating AOSD.

Back to Article Outline

Conflict of interest statement 

We have no conflict of interest.

Back to Article Outline

References 

  1. Bywaters EG. Still's disease in the adult. Ann Rheum Dis. 1971;30:121–133
  2. Singh S, Samant R, Joshi VR. Adult onset Still's disease: a study of 14 cases. Clin Rheumatol. 2008;27(1):35–39
  3. Puchot J, Sampalis JS, Beaudet F, et al. Adult Still's disease: manifestations, disease course and outcome in 622 patients. Medicine. 1991;70:118–136
  4. Mubashir E, Mubashir Ahmed M, Hayat S, Heldmann M, Berney SM. Pulmonary hypertension in a patient with adult-onset Still's disease. Clin Rheumatol. 2007;26:1359–1361
  5. Zen A, Yamashita N, Ueda M, et al. A case of adult Still's disease with pulmonary hypertension. Ryumachi. 1990;30(1):45–52
  6. Padeh S, Laxer RM, Silver MM, Silverman ED. Primary pulmonary hypertension in a patient with systemic-onset juvenile arthritis. Arthritis Rheum. 1991;34(12):1575–1579
  7. Sanchez O, Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary hypertension secondary to connective tissue diseases. Thorax. 1999;54:273–277
  8. Yamane K, Ihn H, Asano Y, et al. Clinical and laboratory features of scleroderma patients with pulmonary hypertension. Rheumatology. 2000;39:1269–1271
  9. Pan TL, Thumboo J, Boey ML. Primary and secondary pulmonary hypertension in systemic lupus erythematosus. Lupus. 2000;9:338–342
  10. Distler O, Pignone A. Pulmonary arterial hypertension and rheumatic diseases – from diagnosis to treatment. Rheumatology. 2006;45:22–25
  11. Galiè N, Torbicki A, Barst R, Dartevelle P, Haworth S, Higenbottam T, et al. Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The task force on diagnosis and treatment of pulmonary arterial hypertension of the European Society of Cardiology. Eur Heart J. 2004;25(24):2243–2278

PII: S1755-0017(08)00099-7

doi:10.1016/j.rmedc.2008.10.002

Respiratory Medicine CME
Volume 2, Issue 2 , Pages 70-72, 2009

Article Tools