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Iranian Journal of Pediatrics
Tehran University of Medical Sciences Press
ISSN: 1018-4406 EISSN: 2008-2150
Vol. 18, Num. 1, 2008, pp. 47-52
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Iranian Journal of Pediatrics, Vol. 18, No. 1, March, 2008, pp. 47-52
Pleuropulmonary Manifestations in Juvenile Systemic Lupus
Erythematosus; A Review and Descriptive Study in 64 Cases
Mohammad Hassan Moradinejad*1, MD, Pediatric Rheumatologist; Sam Chitsaz1, MD
1Department
of Pediatrics, University of Tehran, Medical Sciences, IR Iran
* Correspondence author;
Address: Devisiso of Rheumatology, Children’s Medical Center, Dr Gharib St, Tehran, IR Iran.
E-mail: moradine@tums.ac.ir
Received: 09/04/07; Revised: 20/10/07;
Accepted: 05/12/07
Code Number: pe08007
Abstract
Objective:Juvenile systemic lupus erythematosus (JSLE) is a
multisystemic autoimmune disease that can involve multiple organs such as:
skin, kidney, musculoskeletal system, brain, and others as well as lung.
Pulmonarymanifestations may be an initial and/or life-threatening
complicationof SLE in children. The aim of this report is to
describe the first pleuropulmonary manifestation of
childhood lupus erythematosus.
Material & Methods:We studied retrospectively 64 children with JSLE, diagnosed as
JSLE at the ChildrensMedical Center Hospital between 1995 and2005. All met the American Collegeof Rheumatology (formerly
American Rheumatism Association, ARA)revised criteria for SLE. They
were evaluated for evidence of pleuro-pulmonaryinvolvement.
Findings:During
the 10-yr study period, 64 patients were diagnosedas
childhood-onset JSLE, who had the disease at or before the age of 16 (3-16
years). Fifty five patients (86%) were females and 9 patients (14%) were males
(female: male ratio=6/1). Mean age of thisgroup at the onset of the
disease was 10 years (range 3-16). Eighteen cases (28%) had pulmonary
involvement.Pulmonarycomplications include: infectious
pneumonia in 38%, pleuritis in 33%, pulmonary vasculitis in 11%, and acute
lupus pneumonitis, chronic interstitial pneumonitis and pulmonary embolism
(so-called lupus anticoagulant) each one in 5.5%.
Conclusion: The prevalence of pulmonary involvement in patients with
JSLE varies according to the method used, but clinically significant pulmonary
involvement in our series occurs in approximately 28%. There is few data
regarding the treatmentfor most of the immune mediated pulmonary
manifestations of JSLE.
Key Words:Systemic Lupus Erythematosus,
Lupus Pneumonitis, Chronic Intestinal Pneumonitis, Pulmonary Hemorrhage, Pneumothorax
Introduction
Systemic
Lupus Erythematosus (SLE) is a chronic multisystemic disease, resulting from
tissue damage caused by complementfixing immune complex deposition[1].
SLE mainly affects women (10:1 female to male ratio). Juvenile Systemic Lupus
Erythematosus (JSLE) is not a common illness in the pediatric population. It is
a chronic disorder, which is usually life-long lasting and potentially fatal
disease[2]. Although JSLE has been reported in children in the first
2 decades of life, it is rare in children under 5[3]. The peak
incidence of childhood SLE occurs around puberty and predominantly involves
young women of reproductive age[4]. In 10-20% of JSLE patients,
diagnosis is made for the first time in childhood.[4-5] SLE mayaffect virtually any organ. Predominant manifestations includeskin
manifestations (malar rash, discoid rash, andphotosensitivity),
renal involvement, non-deforming arthritis, serositis, hematological disorders,central nervous system involvement and pleuropulmonary manifestations[6].
Pleuropulmonary
system is one of the most important systems that can be affected in JSLE[7,8].
Pleuritis is the most common pleurapulmonary manifestation, occurring in 30%
of children and may occur with or without pleural effusion[8,9]. Effusion
is usually bilateral and little. Clinical presentations include fever, cough, dyspnea
and pleuretic chest pain[8,9]. Pleural thickeningmay
occur and is reported in up to 50% of chest radiographs taken insymptomatic
patients, but it is unusual in asymptomatic patients[10].
Acute
lupus pneumonitis is uncommon but life-threatening, with an estimated incidence
of 10% in JSLE. The diagnosis is made by exclusion of infection, acute
pulmonary edema, hemorrhage,and infarction. Patients are extremely
ill, febrile, tachypneic,and hypoxic. The chest radiograph reveals
ill-defined bilateralpatchy air space consolidation in the periphery[11,13].
Chronic interstitial pneumonitis (CIP) occurs in 6% of children with JSLE. It
is mild and asymptomatic, but rarely severe cases have been reported with
abnormalities of pulmonary function tests. Infectious pneumonia, is one of the
most common pleuropulmonary manifestations which involves approximately 30% of
patients with JSLE. It is more likely thatthe high infection rate
in JSLE is the result of the immunesuppressive agents usage rather than intrinsicimmune defects.[14] Many dysfunctions have been described in
JSLE, including defects in alveolar macrophage function (such as chemotactic
andphagocytotic activity of neutrophils), decline in T-cell number
and function, and defect in dendritic-cell, B-cell, andnatural
killer (NK) cell function. Opportunistic infection may be life-threatening,
particularly with immuno-suppressivetreatment. Bacteria, viruses or fungi are organisms that can cause
infection in the lung.[14] Sometimes pneumonitis may occur without
infection and is then called non-infectious pneumonitis. Symptoms of
childhood pneumonitis are fever, cough, shortness of breath, and chest pain.[15]
Thromboembolism,
so-called lupus anticoagulant, has been demonstrated in patients with JSLE[16-18],
and it is associated with an increased risk of intravascularthrombosis.
Acute and chronic pulmonary embolism are well recognizedcomplications
of the anticardiolipin antibody existence. Pulmonary hemorrhage is a rare, but
potentially catastrophic, complication of JSLE. Clinical features are
non-specific but diffuse alveolar infiltrates,hypoxemia, dyspnea
and anemia are characteristic. Pulmonary vasculitisoccurs in 7% of
children with JSLE[19], and primary pulmonary vascular disease is
uncommon in these patients. Although the pathogenesis of pulmonary hypertensionremains obscure, multiple factors may play a role; includingpulmonary
vasculitis, thrombosis, and pulmonary artery vasoconstriction.
Pneumothorax,
opportunisticpulmonary infections, and drug toxicity from
immuno-suppressive therapy have been reported in patients with JSLE[18].
Pulmonaryinvolvement is relatively frequent in adult patients rather than
children; the group which pulmonary defects are rarely reported for them.
However, pulmonarymanifestations may be an initial and/or
life-threatening complicationof JSLE in children[16].
Various
laboratory abnormalitieshave been described in JSLE, most commonly
CBC defects (anemia, lymphopenia, and thrombocytopenia), rising ESR and C-reactive
protein (CRP) titer, increased BUN and creatinine, abnormal urinalysis,
positive F-ANA (more than 1:160), antibodiesdirected against
double-stranded DNA (ds-DNA), positive Anti-phospholipide antibodies (APL-ab),
nuclear ribonucleoprotein,Smith (Sm) antigen, anti Ro/SS-A, and
La/SS-B[17,18].
Also,
chest X-ray examination, thoracic computed tomography (CT) scan, pulmonary
fuction test, blood and bronchoalveolarlavage (BAL) sample cultures
has been done. These complications require acomplete and aggressive
approach using appropriate culturesand, if needed, fibreoptic
bronchoscopy, transbronchial biopsyand even open lung biopsy[20-23].
The aim of this report is to
describe the first pleuropulmonary manifestations of childhood SLE.
Material & Methods
We
studied retrospectively 64 children with JSLE, diagnosed as JSLE at the
ChildrensMedical Center Hospital between 1995 and 2005.
We have
classified specific pulmonary lesions in this paper, as we aim to emphasize on
the descriptive evaluation of pulmonaryinvolvement of our patients
with childhood-onset of JSLE.We studied retrospectively
64 consecutive patients with JSLE, either as inpatients or outpatients,
who were followed up by the same attending physicians. All patients met the
American Collegeof Rheumatology (formerly American Rheumatism
Association, ARA)revised criteria for SLE.The patients,
who were diagnosed with JSLE at the ChildrensMedical Center
Hospital between 1995 and2005, were retrospectively evaluated for
evidence of pulmonaryinvolvement. Using a standardizeddata-sheath,
we obtained data regarding the age, sex and presentingcomplaints of
the patients, previous therapies given, clinicaland laboratory
features, treatment and outcome. Informed consentwas obtained from
all patients.
Findings
During
the 10-year study period, 64 patients were diagnosedwith
childhood-onset SLE. All the patients had the disease at or before the age of
16 years (3-16 years). Fifty five patients (86%) from the childhood onset group
were females and 9 patients (14%) were males (ratio =6:1). Mean age of thisgroup of disease onset was 10 years (range 3-16). Table 1 shows Clinical
manifestation of SLE in our patients. Malar rash and musculoskeletal symptom
were the most common symptoms. Eighteen (28%) of JSLE patients had pulmonary involvement, and infectious pneumonia and pleuritis were the most
common pulmonary involvement in our patients. (table 2)
Table 1- Clinical manifestation in 64
children with SLE
Clinical manifestation |
No (%) |
Malar rash |
62 (96%) |
Musculoskeletal |
54 (84%) |
Oral ulcer |
50 (78%) |
Photosensitivity |
45 (70%) |
Hematologic |
40 (62%) |
Renal |
35 (54%) |
pulmonary involvement |
18
(28%) |
cardiovascular |
15 (23%) |
Neuropychiatric |
10
(15%) |
Discoid rash |
10 (15%) |
Table 1- Pulmonary
involvement in 18 patients with SLE
Clinical
manifestation |
No (%) |
Infectious pneumonia |
7 (38%) |
Pleuritis |
6 (33%) |
Pulmonary vasculitis |
2 (11%) |
Pulmonary embolism |
1 (5.5%) |
Acute lupus pneumonitis |
1 (5.5%) |
Chronic interstitial pneumonitis |
1 (5.5%) |
Discussion
SLE is
an autoimmune disease that involves multiple organ systems with various courses
and prognoses[1]. It isnt a common disease in the pediatric
population. Although SLE has been reported in children between 5 to 16 years of
life, it is rare in children under age of 5 years[2]. The peak
incidence of childhood SLE occurs around puberty. In our study, female to male ratio
was 6:1, with a milddifference in comparison with the adult onset
group[3-5]. The mean age of disease
onset in our study was
10 years versus32 years in the adult onset group. A
recent investigation in French children aged 16 years or younger reported an
incidence of 0.22 cases/year/100.000 children with 0.36 girls, and 0.08 boys[5,6].
Even though the survival rate among SLE patients has improved during the past
few decades[7],
there are some host related factors that are associated with death in SLE
patients, including the level of disease activity and demonstrable organ damage
at presentation[8,9].
Moreover,
although pulmonaryinvolvement is relatively frequent in adult
patients; it hasbeen rarely reported in children with SLE. However,
pulmonarymanifestations may be an initial and/or life-threatening
complicationof SLE in children[9,10]. It has been
reported that pleuropulmonary manifestations areseen in
approximately 4050% of patients with JSLE[5-7]. Our retrospective
surveyfor the last 10 yr-data shows 28% patients with JSLE
developed pulmonary manifestations and its less than other studies results in
adult groups[8,9].
Pulmonarycomplications include pleuritis, acute lupus pneumonitis, chronic
interstitial pneumonitis, pulmonary embolism,alveolar hemorrhage,
pulmonary vasculitis,and atypical pneumonia[11].However,
pleurapulmonaryinfections and subclinical lung disease are
relatively commonin childhood-onset SLE[12-14].In
our study infectious
pneumonia and pleuritis
were the most common pulmonary involvement (71%). Sometimes pneumonia is notresolved with antibiotics, because the etiological agent was notdetected.
In This grouppulmonary findings are resolved with corticosteroids
and Azathioprine[26,27]. Because infections are the leading cause of
death in patientswith JSLE, all pulmonary infiltrates in JSLE
should be consideredinfectious until proven otherwise.So,
determining the exact cause requires acomplete and aggressive
approach using appropriate culturesand, if needed, fibreoptic
bronchoscopy, transbronchial biopsy,and open lung biopsy[22-24].
The infectious pulmonary infiltrationsare caused by viruses,
bacteria, fungi and protozoa[14-16].Invasive procedures
to obtain tissue samples for microbiologicaland histopathological
studies can provide valuable informationin lupus lung disorders.
CMV
infectionwas easily detected by non-invasive procedures in our
patients, and lung biopsy was not necessary. All of the few reported patients
with CMV infectionhad pneumonia[20]. Our patients with
CMV pneumonia were successfully treated withGancyclovir.Particularly,
opportunistic infections such as tuberculosis,aspergillosis, and nocardiosis
may only be demonstrated in tissuecultures or histopathological
examinations[20,21].
Acute
alveolar damage with interstitialedema, hyaline membranes and
immune complex deposition in lungtissue has been demonstrated in
patients with acute lupus pneumonitis[17,18].
Conclusion
The
prevalence of pulmonary involvement in patients with JSLE varied with the
method used for diagnosis, but clinically significant pulmonary involvement
occurs in approximately 28% of patients. The pleura-pulmonary manifestations of
SLE range in severity, from the minor pleuritic pain caused by serositis to
life-threateningconsequences of pulmonary hemorrhage. There is
little data regarding treatmentfor most of the immune mediated
pulmonary manifestations of SLE.Moreover, further investigation is
required tofind out the pathogenesis ofSLE pulmonary
complications.
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