Rheumatology Advance Access originally published online on January 20, 2004
Rheumatology 2004; 43: 587-591
Rheumatology Vol. 43 No. 5 (c) British Society for Rheumatology 2004; all rights reserved
Pulmonary involvement in childhood-onset systemic lupus erythematosus: a report of five cases
E. Çiftçi,
F. Yalçinkaya,
E. 
nce,
M. Ekim,
M. leri,
Z. Örgerin,
S. Fitöz1,
H. Güriz,
A. D. Aysev and
Ü. Do
ru
Ankara University Medical School, Department of Pediatrics and 1Ankara University Medical School, Department of Radiology, Ankara, Turkey.
Correspondence to: E. Çiftçi. E-mail: erginciftci{at}doctor.com
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Abstract
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Objective. Systemic lupus erythematosus (SLE) is a chronic systemic
disease, which can involve multiple organs such as kidney, skin
and brain. Lung is another organ that can be affected. A number
of pulmonary complications including pleuritis, pneumonitis,
infectious pneumonia, pulmonary haemorrhage, pulmonary hypertension
and pneumothorax have been reported in patients with SLE. Pulmonary
involvement is relatively frequent in adult patients; it has
infrequently been reported in children with SLE. However, pulmonary
manifestations may be an initial and/or life-threatening complication
of SLE in children. In this paper we aim to emphasize the pulmonary
involvement in childhood-onset SLE via description of our patients.
Methods. The patients, who were diagnosed with SLE at the Children’s Hospital of Ankara University Medical School between 1993 and 2002, were retrospectively evaluated for evidence of pulmonary involvement. All patients fulfilled at least four of the classification criteria of the American Rheumatism Association. Using a standardized form, we obtained data regarding the age, sex and presenting complaints of the patients, previous therapies given, clinical and laboratory features, treatment and outcome. Informed consent was obtained from all patients.
Results. During the 10-yr study period, 16 patients were diagnosed with childhood-onset SLE. Five of them (31%) had pulmonary involvement including acute lupus pneumonitis, invasive pulmonary aspergillosis, cytomegalovirus pneumonia and pulmonary haemorrhage (in two patients). These 5 patients with lupus lung disease are presented in more detail.
KEY WORDS: Systemic lupus erythematosus, Lupus pneumonitis, Invasive aspergillosis, Pulmonary haemorrhage, CMV pneumonia.
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Case 1
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This patient presented with profound respiratory symptoms that
began abruptly 5 days before admission. Her breathing sounds
were diminished and fine crackles were noted bilaterally. Her
body temperature was normal. Chest X-ray examination revealed
bilateral lower lobe consolidation and obliteration of costodiaphragmatic
sinuses (
Fig. 1A). A thorax computed tomography (CT) scan confirmed
the X-ray findings and revealed minimal pleural and pericardial
effusion (
Fig. 1B). The diagnosis of multi-lobar pneumonia was
established. Despite triple antibiotics (vancomycin, ceftriaxone
and clarithromycin) and oxygen therapy, the patient’s
respiratory distress progressed and mechanical ventilation was
required at the fourth day of hospitalization. Blood and bronchoalveolar
lavage (BAL) sample cultures were sterile. Serological tests
for
Mycoplasma pneumoniae and
Legionella pneumophila were negative.
A tuberculin skin test was negative. Although the criteria for
systemic lupus erythematosus (SLE) were found to be incomplete
(
Table 1) corticosteroid treatment was initiated. After this
therapeutic approach, pulmonary symptoms improved rapidly. The
patient was weaned from mechanical ventilation on the 12th day
of hospitalization. Antibiotics were given for 14 days. Pulmonary
infiltration recovered completely, and the patient was discharged
on the 20th day. The patient developed polyarthritis and glomerulonephritis
on follow-up and then the diagnosis of SLE was established.
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FIG. 1. A: Bibasilar infiltrates on chest X-ray. B: Simultaneous thorax CT shows bilateral lower lobe consolidation, and minimal pleural (thin arrows) and pericardial effusion (thick arrow).
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Case 2
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This girl was admitted to the hospital with a history of anasarca
oedema. The diagnosis of SLE was established (
Table 1) and immunosuppressive
therapy was initiated. On the 14th day of therapy, pulmonary
symptoms appeared. Although fine crackles were noted on the
right hemithorax, chest X-ray examination was within normal
limits. Atypical pneumonia was considered, and clarithromycin
therapy was initiated. However, her chest pain persisted and
spontaneous pneumothorax was demonstrated by chest X-ray examination
2 days later (
Fig. 2). Closed tube drainage was performed immediately,
and the therapy was changed to vancomycin, meropenem and fluconazole.
However, her clinical condition deteriorated and a bronchopleural
fistula developed on 4th day of closed tube drainage. A thorax
CT revealed pneumothorax, consolidation, atelectasis and minimal
pleural effusion on the right. The patient was operated on and
the bronchopleural fistula was repaired. A culture from the
excised fistula was positive for
Staphylococcus aureus. Histopathological
examination of excised tissue revealed non-specific inflammatory
changes. Despite treatment with vancomycin, meropenem and fluconazole,
the patient’s fever persisted. Repeated thorax CT revealed
bibasilar consolidation, linear atelectasis and paravertebral
abscesses on the right lung (
Fig. 3). Thorax CT-guided abscess
drainage was performed and
Aspergillus niger was isolated from
the obtained purulent abscess material. Fluconazole was discontinued
and liposomal amphotericin B (L-AmB) 5 mg/kg/day was initiated.
The patient’s fever resolved gradually, and L-AmB dosage
was reduced to 3 mg/kg/day on the 30th day of the treatment
and itraconazole 2
x 200 mg/day was added to the therapy. L-AmB
was discontinued on the 50th day of therapy, and itraconazole
was continued for another 2 months. The patient’s chest
examination and thorax CT were normal at the end of the therapy.
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FIG. 3. Axial CT image demonstrating right-sided linear atelectasis (thin arrow) and paravertebral abscesses (thick arrows).
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Case 3
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This girl was admitted to the hospital with pulmonary symptoms
1 year after the diagnosis of SLE. On admission, fine crackles
were noted at the bottom of both hemithoraxes. Chest X-ray showed
bilateral interstitial infiltration. Cytomegalovirus (CMV) early
antigen, anti-CMV IgM and IgG, and urinary CMV deoxyribonucleic
acid (DNA) were positive. The diagnosis of active CMV infection
and CMV pneumonia was established and ganciclovir therapy 10
mg/kg/day was initiated. The patient’s respiratory symptoms
and pulmonary infiltration were completely resolved by the first
month of ganciclovir therapy. The dose of the drug was reduced
to 5 mg/kg/day orally and continued for 4 months. CMV early
antigen, anti-CMV IgM and urinary CMV DNA were found to be negative
at the follow-up.
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Case 4
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This girl who had been followed with peritoneal dialysis for
3 yr was admitted to our hospital with a 3-day history of pulmonary
symptoms. On admission, she had severe dyspnoea and pallor,
but she had no fever. Fine crackles were noted on both hemithoraxes.
Laboratory examinations included a haemoglobin level of 8.7
g/dl, leucocyte count of 10 100/mm
3 and platelet count of 117
000/mm
3. The erythrocyte sedimentation rate (ESR) was 50 mm/h,
the C-reactive protein level was 0.68 mg/dl, the serum urea
nitrogen level was 159 mg/dl and the serum creatinine level
was 9.4 mg/dl. Chest X-ray examination showed bilateral perihilar
patchy infiltrates. The diagnosis of pneumonia was considered
and ceftriaxone therapy was initiated. However, the patient’s
dyspnoea persisted, her haemoglobin level decreased to 6.7 g/dl,
pulmonary infiltration progressed and haemoptysis occurred.
Coagulation tests were within normal limits and there were no
haemolysis findings. Serological tests for
M. pneumoniae and
L. pneumophila were negative. Because of the unexplained abrupt
decrease in haemoglobin value, haemoptysis and the concomitant
increase in breathing difficulty the possibility of acute pulmonary
haemorrhage was considered. A CT scan of the thorax revealed
bilateral perihilar consolidation that supported the diagnosis
of pulmonary haemorrhage. Haemosiderin-laden macrophages were
demonstrated in BAL samples. BAL sample and blood cultures were
sterile. The girl was treated with corticosteroids and erythrocyte
transfusions. Her clinical condition improved gradually. After
22 days of hospitalization, she was discharged. The patient’s
chest X-ray and chest respiratory examination were normal at
the control visit performed 1 month later.
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Case 5
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This girl with SLE who had been followed for 10 years was admitted
to our hospital with a history of serious respiratory symptoms
and pallor (
Table 1). Laboratory examinations included a haemoglobin
level of 6.7 g/dl, leucocyte count of 9000/mm
3 and platelet
count of 112 000/mm
3. Sedimentation rate and C-reactive protein
level were 40 mm/h and 0.88 mg/dl respectively. She had no fever
and no findings consistent with haemolysis. Because of dyspnoea,
haemoptysis, anaemia and pulmonary infiltration on chest X-ray
examination, pulmonary haemorrhage was considered. The diagnosis
of acute pulmonary haemorrhage was supported by the presence
of haemosiderin-laden macrophages in sputum samples. After the
treatment with corticosteroids and erythrocyte transfusion her
clinical condition improved rapidly. Her chest X-ray returned
to normal at the control visit performed 1 month later.
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Discussion
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It has been reported that pleuropulmonary manifestations are
seen in approximately 50–70% of adult patients with SLE
[
1,
2]. Although pulmonary involvement in SLE has rarely been
systematically investigated in children, pulmonary involvement
is reported to be 5 to 67% [
3–
5]. Our retrospective survey
for the last 10 yr shows that 5 of our 16 patients (31%) diagnosed
with SLE developed pulmonary manifestations. Pulmonary hypertension,
diffuse interstitial disease, pulmonary haemorrhage, pneumothorax,
acute lupus pneumonitis and shrinking lungs have infrequently
been reported in previous studies [
3–
6]. However, pleuropulmonary
infections and subclinical lung disease are relatively common
in childhood-onset SLE [
4,
7].
Our first patient demonstrates that SLE patients might present with pulmonary involvement as the first manifestation. Similarly, Matthay et al. [8] reported that 6 of 12 SLE patients with pulmonary involvement presented with acute lupus pneumonitis at the time of diagnosis. Most of these patients had high fever, dyspnoea, tachypnoea, tachycardia and cyanosis. The most common auscultatory findings were bibasilar fine crackles. The predominant findings on chest X-ray examination were patchy areas of increased density, atelectasis, diaphragmatic elevation and chronic interstitial infiltrates. All patients received corticosteroids and more acutely ill patients received azathioprine. Our first patient had only three criteria for SLE diagnosis including photosensitivity, serositis, and an abnormal titer of antinuclear antibodies (ANA) at the initial evaluation [9]. Because the pneumonia did not resolve with antibiotics, and the aetiological agent was not demonstrated, a diagnosis of SLE was suspected. The patient’s pulmonary findings were resolved with corticosteroids and two other SLE criteria appeared during follow-up. We think that corticosteroid therapy was a lifesaving approach in this patient. We suggest that a high degree of suspicion for the diagnosis of SLE is required in patients with severe pulmonary involvement, even when they do not fulfil the American College of Rheumatology criteria. This approach might enable the initiation of the life-saving corticosteroid therapy as in our patient.
Because infections are the leading cause of death in patients with SLE, all pulmonary infiltrates in SLE should be considered infectious in origin until proven otherwise. This requires a thorough and aggressive approach using appropriate cultures and, if needed, fibreoptic bronchoscopy, transbronchial biopsy and open lung biopsy. The infectious pulmonary infiltrations are caused by viruses, bacteria, fungi and protozoa [1, 10–12]. To the best of our knowledge, approximately 33 SLE patients with invasive aspergillosis have been reported in the English-language literature [13–30]. Most of these patients died and the diagnosis was established during postmortem examination. The similarity between the clinical findings of SLE and invasive aspergillosis was reported as the cause for delayed diagnosis [13]. Our second patient is one of the rare SLE patients with invasive aspergillosis who was diagnosed during the pneumonia episode and was treated successfully. Neutropaenia and immunosuppressive therapy are reported as the leading causes predisposing to invasive aspergillosis in SLE as in our patient [13]. Although the optimal duration of antifungal therapy in invasive pulmonary aspergillosis is controversial, treatment with high-dose amphotericin B for 4–6 weeks or until resolution of neutropaenia or remission of the underlying disease is recommended [31]. Our patient received L-AmB for approximately 7 weeks and itraconazole for 2 months. Our experience underlined that invasive pulmonary aspergillosis must be taken into consideration as a cause of pneumonia in SLE patients. All of the few reported patients with CMV infection had pneumonia and two of these patients died [32–37]. Our patient with CMV pneumonia was successfully treated with ganciclovir. Although it is infrequently reported, CMV infection should not be overlooked in SLE patients with pneumonia.
Pulmonary haemorrhage secondary to SLE is a relatively uncommon and frequently lethal complication. Mortality approaches up to 80% despite the use of high-dose corticosteroids and other immunosuppressive agents [1, 10]. Common clinical features include cough, dyspnoea, fine crackles, severe hypoxaemia and sudden drops in haematocrit levels. Because not all patients demonstrate haemoptysis, a high degree of suspicion is necessary for prompt recognition. Our two patients with pulmonary haemorrhage had cough, haemoptysis and anaemia. Both patients were successfully treated with high-dose corticosteroids and supportive therapy.
Invasive procedures to obtain tissue samples for microbiological and histopathological studies can provide valuable information in lupus lung disease. Bronchoscopy, bronchoalveolar lavage, transbronchial biopsy and open lung biopsy have been previously used [1, 2, 4, 6, 10, 13]. We successfully performed a CT-guided transthoracic needle aspiration in the patient with invasive pulmonary aspergillosis. An open lung biopsy might have been valuable in our first case. Acute alveolar damage with interstitial oedema, hyaline membranes and immune complex deposition in pulmonary tissue has been demonstrated in patients with acute lupus pneumonitis [1, 10]. However, this intervention could not be performed because of the poor clinical condition of the patient. CMV infection was easily detected by non-invasive procedures in our patient 3, and lung biopsy was unnecessary. The diagnosis of pulmonary haemorrhage was clinically obvious in our two patients, and the presence of haemosiderin-laden macrophages supported the diagnosis. We think that lung biopsy was unnecessary and even dangerous in these two patients. There are no well-defined recommendations for lung biopsy indications in SLE patients with respiratory symptoms. We suggest that invasive procedures should be performed to explore the causes of unexplained and unresolved infiltrations. In particular, opportunistic infections such as tuberculosis, aspergillosis and nocardiosis may only be demonstrated by tissue cultures or histopathological examinations [13, 38, 39].
In conclusion, the lung is a major organ involved in childhood SLE, and early diagnosis and appropriate treatment may improve the prognosis.
The authors have declared no conflicts of interest.
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Submitted 24 June 2003;
revised version accepted 25 November 2003.
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Abstract
Case 1