19 May 2021: Articles
Simultaneous Onset of Pulmonary Infection and Systemic Lupus Erythematosus: A Case Report
Unknown etiology, Challenging differential diagnosis, Rare coexistence of disease or pathology
Dario Bruno1EF, Giacomo Tanti1F, Antonella Cingolani23D, Francesco Ria45D, Elisa Gremese16ACDEF*, Luisa Mirone16AEFDOI: 10.12659/AJCR.929866
Am J Case Rep 2021; 22:e929866
Abstract
BACKGROUND: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease resulting from dysregulation of the immune response. In genetically predisposed subjects, infections reputedly trigger an immune activation leading to autoimmunity and overt autoimmune diseases such as SLE.
CASE REPORT: We report the case of a 19-year-old woman who presented to our hospital reporting high-grade fever, dry cough, and polyarthralgia despite a course of empiric antibiotic and steroid therapy administered by her general practitioner (GP). On physical examination, she had a malar rash, a palpable erythematous maculopapular non-itchy rash over the limbs and trunk, and mild polyarthritis. A contrast computed tomography (CT) scan of the chest showed a pulmonary right upper-lobe consolidation with air bronchogram and multiple necrotizing conglomerate mediastinal lymph nodes. Culturing of collected samples from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) of the mediastinal lymph node revealed growth of Mycobacterium kansasii. Antinuclear antibodies (ANA) and lupus anticoagulant (LAC) were positive. A diagnosis of M. kansasii infection associated with SLE was made. She was started on anti-mycobacterial and hydroxychloroquine therapy and entered into a joint rheumatological and infectious disease follow-up. Six months later, a CT scan with positron emission tomography (PET) showed a significant reduction in size of the basal right upper-lobe consolidation and hypermetabolic activity in multiple pulmonary areas and mediastinal lymph nodes. ANA and LAC tests were repeated and remained positive. The decision was made to continue the ongoing therapy course for 1 year in total.
CONCLUSIONS: Clinical and experimental studies have suggested the association of mycobacterial infections with SLE and as a possible infectious trigger of autoimmunity. We describe a unique case of M. kansasii infection associated with the onset of SLE in a young woman.
Keywords: Autoimmunity, Lupus Erythematosus, Systemic, Mycobacterium Infections, Nontuberculous, case reports, Endoscopic Ultrasound-Guided Fine Needle Aspiration, Lymph Nodes, Mediastinum, Mycobacterium kansasii, young adult
Background
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease resulting from chronic and recurrent activation of the immune response and characterized by the production of autoantibodies to nuclear antigens. Clinical and experimental evidence support the role of infections in the induction of SLE. Infections may participate in the break of tolerance and in triggering autoimmunity by various mechanisms [1]. Molecular mimicry, cross-reactivity, over-expression of type 1 interferon (IFN) genes, and bacterial and viral hypo-methylated DNA are suggested mechanisms of autoimmunity induction.
Nontuberculous mycobacteria (NTM) are ubiquitous environmental microorganisms usually embedded in water and soil. NTM infection is increasing worldwide and although immuno-suppression significantly contributes to the risk of infection, in recent years the disease is also spreading in immunocompe-tent human recipients, in which about 77% is pulmonary [2].
In the last century, the possibility that mycobacterial infections could trigger autoimmune diseases was suggested. A specific relationship between mycobacteria and autoimmunity was pointed out based on the observation that the generation of autoreactive T cells was initially stimulated by exposure to the immunodominant protein antigens of mycobacteria and that patients with pulmonary tuberculosis developed sets of antinuclear antibodies characteristic of patients with SLE [3]. Furthermore, monoclonal anti-TB antibodies binding the glycolipids of part of the mycobacterial cell wall were found to react with ssDNA, dsDNA, and anti-DNA autoantibodies from SLE patients [4].
So far, 2 clinical studies have supported a possible role of mycobacterial tuberculosis (TB) in precipitating SLE in genetically predisposed patients [5,6]. In 2004 Takada and colleagues described a case of atypical mycobacterial infection from the
Case Report
A 19-year-old woman was admitted to our department on October 11, 2019 because of high-grade fever (body temperature up to 39.5°C), dry cough, and polyarthralgia. Six weeks before admission, she had experienced fever with occasional cough and general malaise. On general practitioner (GP) advice, she had undergone chest radiography, which showed a right upper-zone haziness and she was administered a 10-day course of levofloxacin (750 mg/day) with no relief of symptoms.
She was then started on oral prednisone (25 mg/day gradually tapered to withdrawal) with a transient improvement in her symptoms. Two weeks later, she experienced fever again and was therefore admitted to the hospital.
On physical examination, she had a malar rash, a palpable erythematous maculopapular non-itchy rash over the limbs and trunk, and mild swelling and tenderness in her wrists, metatarsal-phalangeal joints, ankles, and right knee. Laboratory analysis on admission revealed a leukocyte count of 2.38×109/L (neutrophils 1.72×109/L; lymphocytes 0.57×109/L); hemoglobin 7.3 g/dL; platelet count 176×109/L; gamma-glutamyltransferase 69 IU/L (reference range: 5–36 IU/L); ferritin 1489 mg/dL; C-reactive protein (CRP) 231.7 mg/L; and erythrosedimentation rate (ESR) 120 mm/h. C3 and C4 complement fraction serum levels, lactate dehydrogenase (LDH), and serum β2 microglobulin were within normal limits. She was detected to be positive for both antinuclear antibodies (ANA) by immunofluorescence (IF) at 1: 320 titer with a speckled pattern and lupus anticoagulant (LAC), with a dRVV ratio of 1.79 (normal range 0.70–1.25). Antibodies to RNP, Sm, SS-A/Ro, SS-B/La, Jo-1, Scl-70, cardiolipin, and beta2GPI were all negative. Myeloperoxidase antineutrophil cytoplasmic antibody (ANCA) and proteinase 3 ANCA were both negative. Histology from a 4-mm punch biopsy of right gluteous skin lesions showed evidence of a granulocytic infiltrate with karyorrhexis in papillary derma (Figure 1A, 1B).
Virus profiles including HIV, hepatitis B virus, hepatitis C virus, cytomegalovirus (CMV), and Epstein-Barr virus (EBV) were negative. Multiple blood cultures were collected and all failed to grow bacteria, mycobacteria, or fungi. Urine and bone marrow cultures grew no organisms. Mantoux and QuantiFERON tuberculosis (TB) spot were negative.
A chest radiograph showed an opacity in the right upper pulmonary lobe without cavity, and bilateral sub-pleural nodular infiltrates in the upper lobes. Contrast computed tomography (CT) scans of the chest, abdomen and pelvis showed left pleural effusion, pulmonary right upper-lobe consolidation with air bronchogram and multiple necrotizing conglomerate mediastinal lymph nodes (Figure 2A).
Both transthoracic (TTE) and transesophageal echocardiography (TEE) showed a posterolateral and anterior pericardial effusion (0.5 cm). Fluid from a bronchoalveolar lavage (BAL) showed no evidence of acid-fast bacilli (AFB) on staining and culture. The patient underwent an endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) of the mediastinal lymph node. A molecular positivity for NTM was observed in collected samples. Further culturing revealed growth of
Discussion
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by production of autoantibodies and multi-organ damage. Activation of both the innate and the adaptive immune systems occurs in SLE, leading to the breach of self-tolerance and the emergence of autoreactive T cells. Chronic infections can activate autoreactive B cells and can induce their differentiation into memory cells, thus initiating autoimmunity in genetically predisposed subjects [1].
Since the late 1980s, the literature has suggested an association of mycobacterial infections with SLE and as a possible infectious trigger of autoimmunity. Mycobacterial infections cause an immune activation in which the innate immune system seems to play a key role in driving the autoimmune process. In 1988 Young and colleagues demonstrated that the immunodominant protein antigens of mycobacteria are stress or heat shock proteins (HSPs) [8]. When a process of infection occurs, both the microorganism and the invaded host cells respond by producing high levels of stress proteins. Based upon the observation that HSPs of
The hypothesis of
The incidence of
Unlike the case reported by Takada et al, in our case
The diagnosis of
Conclusions
We present a unique case of
Figures
Figure 1.. Erythematous maculopapular rash on the lower right limb (A); Granulocytic infiltrate with karyorrhexis in the papillary derma (B). Figure 2.. Contrast computed tomography (CT) comparison images of the pulmonary right upper-lobe consolidation with air bronchogram upper-lung infiltrates at the time of hospital admission (A) and after 6 months of treatment (B). Figure 3.. 18Fluorodeoxyglucose PET/CT scan at 6 months follow-up, showing increased, not heterogeneous, radiotracer uptake within the right upper pulmonary lobe and multiple bilateral paratracheal, subcarinal, and hilar lymph nodes.References:
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