Clin Rheumatol (2005) 24: 415–419 DOI 10.1007/s10067-004-1047-8

CASE REPORT

O¨mer Nuri Pamuk Æ Orbay Harmandar Æ Birsen Tosun Yener Yo¨ru¨k Æ Necati C¸akır

A patient with ankylosing spondylitis who presented with chronic necrotising aspergillosis Report on one case and review of the literature

Received: 2 March 2004 / Accepted: 18 October 2004 / Published online: 23 December 2004 Ó Clinical Rheumatology 2004

Abstract Upper lobe fibrobullous disease is a wellknown finding in advanced stages of ankylosing spondylitis (AS). In this report, we present a 57-year-old male patient who was diagnosed with a right apical cavitary lesion after coming to us with the complaint of haemoptysis. The patient underwent upper lobe segmentectomy and an aspergilloma was detected. Histologic findings were in favour of necrotising Aspergillus pneumonia. It was interesting that the patient had not been diagnosed with AS before and presented initially with chronic necrotising Aspergillus pneumonia. In the literature, there are recently published series of pulmonary high-resolution computed tomography (HRCT) in AS which claim that parenchymal abnormalities are quite frequent. Although the clinical significance of these abnormalities is not known with

O¨. N. Pamuk (&) Æ N. C¸akır Department of Rheumatology, Trakya Medical Faculty, University of Trakya, Edirne, Turkey E-mail: [email protected] E-mail: [email protected] Tel.: +90-284-2350001 O. Harmandar Department of Internal Medicine, Trakya Medical Faculty, University of Trakya, Edirne, Turkey B. Tosun Department of Pathology, Trakya Medical Faculty, University of Trakya, Edirne, Turkey Y. Yo¨ru¨k Department of Chest Surgery, Trakya Medical Faculty, University of Trakya, Edirne, Turkey N. C¸akır Altunizade, Okul Sokak, Erzurum Sitesi, No: 19/5 U¨sku¨dar, Istanbul, Turkey

certainty, it has been reported that they might be seen even in early-stage patients. It is suggested that the pulmonary involvement in AS might be affected by mechanical factors related to limitation of motion of the thoracic cage and also by parenchymal inflammation. Here, we review the series of pulmonary HRCT in AS patients. Keywords Ankylosing spondylitis (AS) Æ Aspergillosis Æ Fibrocavitary disease Æ High-resolution computed tomography (HRCT)

Introduction The most commonly observed lesion during the course of ankylosing spondylitis (AS) is upper lobe fibrobullous disease and it is generally seen in advanced stages [1]. Although it is usually asymptomatic, it might radiologically resemble tuberculosis and excavated neoplasm [1, 2]. In addition, apical fibrobullous areas might form the background for Aspergillus localisation [3, 4]. Until recently, it was thought that pleuroparenchymal involvement in AS was a rare extraskeletal finding [5]. However, with the more frequent use of high-resolution computed tomography (HRCT) for the evaluation of lung parenchyma, this idea has to be reconsidered. Series reporting on HRCT findings in AS in recent years suggest that pulmonary parenchymal abnormalities are more frequent than anticipated [6–12]. However, the clinical significance of these abnormalities is unclear. In this report, we present one patient who had inflammatory back pain for a long time, who presented with pulmonary symptoms and who was later diagnosed with chronic necrotising Aspergillus pneumonia and AS. In addition, we review series of AS patients who had pulmonary involvement based on HRCT findings.

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Case report A 57-year-old male patient came to the emergency department of our hospital with the complaints of cough and recurrent haemoptysis in the last 3 months. The patient who had fatigue and malaise for the last 1.5 years had been smoking one pack of cigarettes/day for 30 years. The initial physical examination revealed a blood pressure of 110/70 mmHg, pulse rate of 76/min

Fig. 1 Chest X-ray shows a cavitary lesion in the upper lobe of the right lung

Fig. 2 Necrotising Aspergillus pneumonia in the fibroinflammatory pulmonary parenchyma is seen (haematoxylin and eosin stain)

and the patient appeared cachectic. Auscultation revealed crepitant rales over the upper zones of the right lung. Laboratory studies were as follows: erythrocyte sedimentation rate (ESR) 102 mm/h, C-reactive protein (CRP) 10 mg/dl, haemoglobin 10.6 g/dl, leucocytes 9300/mm3, platelets 554,000/mm3, total protein 6.4 g/dl and albumin 2.6 g/dl. Other biochemical tests, electrolytes and urinalysis were within normal limits. Pulmonary function tests (PFT) revealed a forced vital capacity (FVC) of 1.93 l (57% of predicted), forced expiratory volume in 1 s (FEV1) of 1.9 l (70% of predicted) and carbon monoxide diffusion capacity (DLCO) of 23 ml/ min per mmHg (43% of predicted). Chest X-ray showed a right upper cavitary lesion (Fig. 1). The gram staining and Ehrlich-Ziehl-Neelsen (EZN) stain of the sputum revealed no pathogen; sputum culture remained sterile. The tuberculin skin test was positive (with 18 mm induration). Thorax CT demonstrated a cavitary nodular lesion in the posterior segment of the right upper lobe. Based on tuberculin skin test positivity and CT findings, the patient was started on antituberculosis therapy with four agents. After 2 months of antituberculosis therapy, the patient’s haemoptysis persisted and he had gastrointestinal symptoms due to the drugs. Bronchoscopy was planned; however, the patient had massive bleeding and could not tolerate the procedure. Therefore, right upper lobe apical and posterior segmentectomy was undertaken. Macroscopically, there was a 6-cm cavitary lesion containing an aspergilloma in the defined localisation, and the peripheral pulmonary tissue was atelectatic. Histopathologic examination showed a cavitary lesion around which there was granulation tissue consisting of many eosinophils, mononuclear inflammatory cells and vessels. On the side facing the lumen, there was prominent necrosis and fungal hyphae were seen (Fig. 2). There was an increase in

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interstitial connective tissue and mononuclear inflammatory cell infiltration in other pulmonary areas. The patient was diagnosed with upper lobe fibrocavitary disease and Aspergillus superinfection, and antituberculosis therapy was discontinued. Four months after the operation, the patient came to our Rheumatology Department with the complaints of pain and swelling of the right knee and both ankle joints. His past medical history had revealed back pain of inflammatory character for 30 years and he admitted using various nonsteroidal anti-inflammatory drugs (NSAIDs) when his pain increased. His pain and morning stiffness regressed during the last 10 years; however, his spinal movements became prominently more limited. On physical examination, chest wall expansion was decreased, forward bending of the lumbar spine was limited and he had kyphosis. The range of motion of the cervical spine was limited prominently, the pelvis was anteverted and there were flexion deformities of the elbows. There was warmth and swelling of the right knee joint, and there were arthritides in both ankle joints. The examination of the synovial fluid obtained from the right knee joint showed no pathogens and the cultures remained sterile. Pelvis X-ray revealed bilateral grade IV sacroiliitis, and there were syndesmophytes and vertebrae with a bamboo appearance on spinal X-rays. With all the available clinical and radiographic findings, the patient was diagnosed with AS. His peripheral arthritides regressed with NSAIDs, and sulphasalazine was added to the treatment regimen. The patient is healthy after 6 months of follow-up.

Discussion Fibrobullous disease is a late complication of AS: it is characterised by slowly progressive fibrosis of the upper pulmonary zones and develops nearly 2 decades after the onset of AS [6]. It is seen as linear or patchy opacities on chest X-ray and later a cavity with cystic appearance develops. These cavities might be colonised with Aspergillus [1, 9]. Our patient had upper lobe fibrocavitary disease and later developed Aspergillus superinfection in the cavity. Chronic necrotising Aspergillus pneumonia was confirmed histopathologically; however, we could not determine its exact classification because the cultures were negative. It has been reported that the presence of Aspergillus antibodies in the serum support the diagnosis and are positive in 83–100% of cases [13]. We could not perform these tests because they were unavailable at our centre. Our case was interesting because although the patient’s clinical radiographic findings were typical, he had not been diagnosed with AS for a long time and he presented with haemoptysis and constitutional symptoms. Although some studies [2] reported chronic Aspergillus colonisation in a significant proportion of AS patients (50–65%), symptomatic pulmonary Aspergillus

infection is rare [1]. In one AS series, pleuroparenchymal manifestations were detected in 28 of 2080 patients (1.3%) and most of these were associated with upper lobe fibrobullous disease [1]. Aspergillomas were detected in 5 of those 28 patients (0.24%). Cases of pulmonary aspergillosis have also been reported—although less frequently than in AS—in rheumatoid arthritis (RA) localised in rheumatoid nodule-associated cavities [14] and in systemic lupus erythematosus (SLE) patients using high doses of immunosuppressive drugs [15]. Recent studies showed that pulmonary findings, other than fibrobullous disease, might be seen in AS. This is because of HRCT being used, which is an especially sensitive method for evaluating the pulmonary parenchyma. Table 1 summarises recent studies on HRCT in AS patients. Here, the factor which draws most attention is that there is a high frequency of HRCT abnormalities in patients with normal chest X-rays. When we consider all HRCT series summarised in Table 1, we see that upper lobe fibrosis was detected in 11 of 220 cases; however, aspergilloma was present in only 1 case. Pathologies such as upper lobe fibrosis/cavity formation, which might have clinical significance, are seen in rather late stages of AS. This is supported by these findings being absent in two studies in Table 1 which included AS patients with relatively shorter disease duration—less than 15 years [8, 10]. Our patient had a cavitary lesion and a 30-year history of inflammatory back pain. However, probably some pulmonary changes—other than cavities—occur in early disease stages and they progress with time. This was demonstrated in two recent studies [9, 10]. The clinical significance of abnormalities detected by HRCT or PFT in studies presented in Table 1 is not clear. Although HRCT abnormalities were frequent in the patients, impaired PFTs were encountered less often. The percentage of lung-related symptoms is even lower as seen in Table 1. Therefore, we might conclude that most of the abnormalities on thorax HRCT in AS do not cause clinical symptoms. There are different explanations for the presence of an increased frequency of HRCT abnormalities in AS patients. One study [8] claimed that mechanical reasons such as thoracic cage rigidity were responsible for the restrictive problem. Contrarily, two different studies [6, 12] stated that the pulmonary findings in AS were inflammatory and not mechanical. In addition to limitation of thoracic cage movements, probably interstitial inflammation plays an important role in pulmonary lesions [16]. The treatment for symptomatic aspergilloma is administration of antifungal drugs. In cases where medical therapy is insufficient, there is an indication for thoracic surgery [2]. Haemoptysis, a common symptom, is experienced by the vast majority of patients with aspergilloma [17]. As the prognosis of symptomatic aspergilloma is poor, surgical resection is indicated in such cases [18]. Our patient underwent thoracic surgery and a cure was obtained.

Casserly et al. [6] diagnosed ILD in four patients and two had apical fibrosis. They suggested that AS-related pulmonary findings were inflammatory rather than mechanical. In this study HRCT, PFT findings and symptoms were found correlated in subjects with interstitial lung disease (ILD) b In the study of Fenlon et al. [7], 88% of the patients were ex-smokers or current smokers. Four patients had nonapical ILD, three of them had restrictive ILD and two were current smokers c Turetschek et al. [8] found no correlation between HRCT abnormalities and functional and clinical findings. They concluded that restrictive abnormalities were predominantly because of mechanical factors d S¸enocak et al. [9] detected pulmonary parenchymal changes on HRCT which started in the early period and increased with disease duration. Although cigarettes were claimed to have a role, interstitial inflammation was mainly responsible for the lesions e Kiris et al. [10] included patients with disease duration of less than 10 years. They found increased incidence of small airway disease in early-stage AS f El-Maghraoui et al. [12] confirmed that the chest HRCT of patients with AS showed a great number of abnormalities undetectable by X-rays. No correlation was noted between HRCT and PFT. There was a significant correlation between PFT and symptomatic and structural severity parameters of AS. Only apical fibrosis and bronchiectasis were significantly more frequent with increasing disease duration. Smoker and non-smoker groups did not show any significant difference in HRCT abnormalities or in PFT results

a

10 ? 6 NA 10 4 NA 2 ? 0 NA NA NA NA 6 8 12 6 12 8 19 10 ? 12 8 12 10 21 1 ? 0 0 0 0 0 2 ? 0 3 0 3 5 19 18 15 17 18 25 29 4 4 0 NA 0 2 2 14+9 88% 0 7+3 9+2 NA 20 6 ? 0 NA 6 NA NA 18.5 ? 13 15.6 7.0 NA 7.5 44.8 1.2–48 43 39.7 30.8 NA 37.6 26 26 21 20 28 44 55 Casserly et al.a [6] Fenlon et al.b [7] Turetschek et al.c [8] S¸enocak et al.d [9] Kiris et al.e [10] El Maghraoui et al. [11] El Maghraoui et al.f [12]

19 ? NA 18 22 NA 90.9%

Age Duration Symptomatic Smoking X-ray HRCT Upper Aspergilloma PFT Restrictive DLCO PFT+HRCT (mean) of disease patients (n) abnorm. abnorm. lobe abnorm. abnorm. abnorm. abnorm. (years) fibrosis Sex (male) n References

Table 1 Series reporting on pulmonary HRCT findings in AS patients. NA not available

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The upper lobe fibrocavity formation and Aspergillus superinfection present in our case are rare complications which might be seen in advanced stages of AS. Generally, AS is a progressive disease with an insidious course and clinical findings might be misleading and noninformative for a long time; therefore, the diagnosis might be delayed. Similar to our case, patients might rarely present with pulmonary symptoms. With the use of HRCT becoming more common in recent years, it is now understood that the lungs are involved quite commonly even in early stages of AS. However, there are different ideas about the clinical significance and pathogenesis of pulmonary findings seen during the course of the disease and these should be clarified.

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