Positive HIV Screening Test in a Patient with Rapidly Progressive Interstitial Lung Disease: A Case Report

Introduction

Interstitial lung diseases (ILDs) refer to a group of diffuse lung parenchymal diseases with high morbidity and mortality that can occur in various types of connective tissue diseases, including rheumatoid arthritis, systemic lupus erythematosus, polymyositis or dermatomyositis (DM), and mixed connective tissue disease.^1,2 Clinical amyopathic dermatomyositis (CADM), a distinct subclass of DM, is characterized by typical skin manifestations without muscle weakness, along with usually normal creatine kinase (CK) levels and electromyographic findings.³ Patients with CADM are sometimes affected by rapidly progressive ILD (RP-ILD), which can be fatal, is resistant to immunosuppressive treatments, and carries a high mortality rate.^4,5 In addition, 60–70% of patients with CADM have anti-melanoma differentiation-related gene 5 (anti-MDA5) antibodies,⁶ which have been reported to be associated with severe, progressive, and often fatal ILD.

We herein describe a patient with anti-MDA5 antibody-associated CADM complicated by RP-ILD, who was initially found to have a false-positive HIV screening result. It is easy for this condition to be misdiagnosed as PCP, which is the most common opportunistic infection in people living with HIV (PLWH). This case is reviewed to discuss the diagnostic and therapeutic process of CADM-associated ILD in the context of a false-positive HIV screening result.

Case Report

A 47-year-old man developed recurrent fever and progressive dyspnea in February. Outpatient tests revealed no abnormalities in routine blood work or respiratory pathogen antibody testing. He was initially diagnosed with pneumonia based on chest CT findings 10 days after the onset of illness, and was treated with empiric antibiotics for a week without improvement. He was then hospitalized for further treatment. After hospitalization, laboratory tests revealed elevated C-reactive protein, procalcitonin and lactate dehydrogenase, decreased partial pressures of carbon dioxide (PaCO₂) and oxygen (PaO₂) (Table 1). Pulmonary function tests revealed restricted ventilation dysfunction with a moderate reduction in oxygen diffusion capacity. Chest CT findings suggested severe ILD, characterized by diffuse ground-glass opacities, reticular patterns, patchy infiltrates, and bronchovascular bundle thickening in both lungs (Figure 1 A-C). Before proposing a bronchoscopic examination, infectious disease screenings, including HIV, HBV, HCV, and syphilis, were performed as part of the preoperative assessment. Notably, it was found that the patient’s HIV screening test was positive, with a CD4⁺ T cell count of 241 cells/μL, which decreased to 189 cells/μL 5 days later. HIV viral load was persistently undetectable, and the levels of serum (1, 3)-β-d-glucan and lactate dehydrogenase were elevated (Table 1). The patient was initially suspected of PCP, the most common opportunistic infection in people living with HIV, based on his clinical presentation, laboratory results, and CT findings. Despite 5 days of anti-PCP treatment, his condition did not improve; pneumocystis jirovecii was not detected in the sputum sample, and follow-up HIV nucleic acid tests were both negative (Table 1). The patient’s pulmonary condition rapidly worsened. Additionally, he recalled the onset of a scalp rash one month prior, raising concern for interstitial lung disease associated with dermatomyositis. Finally, CADM was suspected based on myalgia-free facial rashes and normal serum levels of CK. Critically, the anti-MDA5 antibody was strongly positive, confirming the diagnosis of CADM and predicting a grave prognosis. Once diagnosed, the patient was treated with immunosuppressive drugs, including intravenous glucocorticoids, immunoglobulins, and oral tacrolimus. However, the treatment failed, and the patient died on the ninth day of hospitalization.

Table 1 Laboratory Test Results on Admission

Figure 1 Chest computed tomography (CT) scan. (A) Sagittal chest CT scan shows bilateral thoracic cage is symmetrical, diffuse ground-glass opacities and reticular patterns are observed in both lungs; (B) Coronal view demonstrates bronchovascular bundle thickening in both lungs, with diffusely distributed ground-glass opacities and reticular patterns. Bilateral pleural thickening is also observed; (C) Multiple ground-glass opacities are observed in the subpleural regions and along the bronchovascular bundles in both lungs, accompanied by localized interlobular septal thickening, most pronounced in the subpleural areas, patchy consolidations and air bronchograms are also visible.

Discussion

The false-positive result of the HIV screening test complicated the diagnostic and treatment process in this patient. By sharing this case, insights are provided for clinical practitioners, highlighting the challenges posed by false-positive results in HIV testing and the importance of further evaluation and confirmation before treatment decisions are made.

Diagnosis of CADM can be challenging in certain patients, as they may lack characteristic muscle manifestations and exhibit atypical skin lesions following hospitalization. In addition, CADM-associated RP-ILD is associated with a high mortality rate, underscoring the importance of early identification and effective management of these individuals. As demonstrated in our reported case, the patient with a positive anti-MDA5 antibody status presented with rapidly progressive and ultimately fatal ILD. Currently, there is a lack of randomized controlled trials evaluating treatments for ILD associated with MDA5 antibody-positive CADM. Existing studies suggest that early administration of high-dose systemic corticosteroids in combination with other immunosuppressants, such as calcineurin inhibitors and/or cyclophosphamide, may offer the most significant survival benefit for patients with RP-ILD.^7,8 Additionally, tofacitinib and rituximab may provide benefit for refractory rashes and RP-ILD in MDA5-DM patients.^9,10 Given the high mortality risk in this population, early diagnosis and intervention are critical.

False-positive HIV screening tests in CADM patients have not been previously reported. The current 4th generation HIV test, which is the leading method for HIV screening, narrows the window period by identifying HIV-1/2 antibodies and HIV p24 antigens with sensitivity and specificity above 99%.¹¹ However, misdiagnosis of the 4th generation HIV test has been reported in some cases. For example, Sethi et al have demonstrated for the first time that SARS-CoV-2 antigen/antibody exhibits cross-reactivity with commercial chemiluminescence immunoassay methods, leading to false positive results.¹² Moreover, autoimmune diseases such as SLE and RA, pregnancy, viral infections, and hematologic malignancy may result in false-positive HIV tests.^13–16 Therefore, it is speculated that false-positive HIV screening may be related to CADM or DM due to cross-reactivity of antigens. As an autoimmune disease, the pathogenesis of DM is complex and not yet fully clarified and involves genetic, environmental, and immune mechanisms. The genetic association of DM is primarily related to human leucocyte antigen (HLA) class II alleles, supporting the role of an immune response driven by T cells.^17,18 Interestingly, autoimmunity during HIV-1 infection contributes to titers of autoantibodies to HLA molecules and increases other surface markers of CD4⁺ T cells.¹⁹ Given the immunopathogenesis of CADM/DM and HIV, it is hypothesized that the immune response to CADM/DM is likely to exhibit immune activation that cross-reacts with HIV antigens, further contributing to HIV false positives. The limitation of our report is the lack of retained participant samples for further validation, which prevents us from determining whether the false positives in HIV testing were attributable to antibody cross-reactivity.

Conclusion

In summary, anti-MDA5 antibody-positive CADM with RP-ILD as the primary manifestation is a rare clinical entity with a dismal prognosis and high mortality. While the immune response can result in false-positive HIV screening due to antigen cross-reactivity, this may lead to delayed diagnosis of CADM and ILD. In light of this reported case, it is essential to acknowledge the importance of conducting a thorough assessment of factors beyond HIV-related conditions in individuals with no history of HIV exposure but who test positive on HIV screening. This necessitates a comprehensive investigation into alternative underlying causes.