Symptoms, X-ray findings point to COVID-19, but not

A 43-year-old Indian man consulted an emergency department in Doha, Qatar, who said he had fever, headache, low energy, shortness of breath, and had cough and flu symptoms for about a week. Symptoms like.

On physical examination, his temperature was 39°C, basic crackling in both lungs, and oxygen saturation in room air was 91%. The rest of the medical examination is not surprising.

Patients say he was diagnosed with tuberculosis (TB) meningitis about two months ago and was being treated. About two weeks before this latest visit, he developed drug-induced hepatitis and his first-line drug was moxifloxacin 400 mg po once/day, cycloserine 500 mg po twice/day, Rifampicin 600 mg was switched to oral anti-tuberculosis treatment. Once daily, ethionamide 500 mg orally once daily, pyridoxine 50 mg orally once daily.

He was admitted to the hospital and continued to be sprayed and aerial isolated according to the COVID-19 protocol and possible SARS-CoV-2 infection or pulmonary tuberculosis.

Laboratory tests are normal for white blood cell count, eosinophils, procalcitonin, kidney and liver function tests, and electrolytes. However, his C-reactive protein is significantly elevated, at 109.2 mg/L compared to the normal range of 0-5 mg/L.

Chest x-ray reveals bilateral lung infiltrates and bilateral patchy integration. The patient’s file shows that this was not observed on a previous chest x-ray taken when he was diagnosed with tuberculous meningitis.

Clinicians are unlikely to consider heart failure because the patient is not clinically overloaded. The first workup for infections is bacterial growth ( Mycoplasma pneumoniae, Legionella pneumophila, And Chlamydia pneumonia). Nasopharyngeal Polymerase Chain Reaction (PCR) tests eliminate the possibility of infection with common respiratory viruses such as influenza, parainfluenza, respiratory syncytial virus, and Middle East respiratory syndrome coronavirus.

In the light of respiratory symptoms in patients with an ongoing COVID-19 pandemic, clinicians performed two SARS-CoV-2 nasopharyngeal reverse transcription (RT)-PCR tests at 24-hour intervals, both negative Returns the result.

Mycobacteria (AFB) smears are tested by PCR and sputum cultures are tested to rule out negative tuberculosis reinfection or drug resistance with negative results.

The team also considers the possibility of acute eosinophilic pneumonia, but believes it is not because the patient is a non-smoker and his leukocyte fraction including eosinophils is normal .. Hypersensitivity pneumonia is also considered unlikely because the patient has not been exposed to animals or birds.

The HIV/p24 antigen combination test is non-reactive.

The clinician will begin the patient with empirical antibiotic therapy and continue the ongoing treatment with 2 L of supplemental oxygen through the nasal cannula.

Over the next few days, the patient continues to have a fever and further investigations include computed tomography (CT) scans of the abdomen and chest. His CT chest shows obscure perihilar and peribronchial opacities and patchy areas of alveolar solidification.

The scan reveals ground-glass opacities at the base of the lungs, with small pleural thickenings and lymph nodes less than a few centimeters in the mediastinum. A speckled integration and bronchiogram is also recorded, consistent with acute respiratory distress syndrome (ARDS).

Five days after the patient’s hospitalization, the clinician orders a bronchoscopy and sends a bronchoalveolar lavage (BAL) and tissue sample for further analysis.

Results show predominant lymphocytes (63% lymphocytes, 20% neutrophils, 16% macrophages), but are negative in AFB and bacterial, viral, and fungal cultures. PCR Pneumocystis Girovechi SARS-CoV-2 is also negative and BAL analysis excludes alveolar hemorrhage.

Histopathology identifies enlarged interstitial septa with loose connective tissue and several chronic inflammatory cells including lymphocytes, histiocytes, and rare eosinophils, but evidence of dense fibrosis there is no.

In addition, the alveolar canals and sac are filled with organizing fibrous material and there is evidence of type II pneumocyte hyperplasia, but no granulomas, vasculitis, viral inclusions, fungal elements, or malignancy.

Based on all the findings, clinicians suspect that the patient’s pneumonia is drug-induced and that the drug rifampicin is likely based on the patient’s clinical presentation, histology, and available data. The team will discontinue the patient’s rifampicin and start steroid therapy 6 days after admission (prednisolone 40 mg po once/day). Other anti-TB drugs will continue.

Stopping rifampicin effectively relieves the patient’s symptoms. The fever is resolved by the second day of steroid treatment and oxygen saturation in the room is maintained normally. He was asymptomatic, discharged home with a three-week tapering steroid regimen, and is scheduled for follow-up at a medical and infectious disease clinic.

Two weeks later, the patient appears in the tuberculosis clinic and has no symptoms yet. Attempts to reintroduce rifampicin revert to previous symptoms and confirm the diagnosis of rifampicin-induced pneumonia.

One month after discharge, at follow-up in the clinic, the patient is afebrile and asymptomatic, maintains room oxygen saturation, and chest X-ray does not completely invade the lungs Is shown.

Debate

Clinician reporting this If In the case of rifampicin-induced pneumonia, clinical and radiological resemblance to COVID-19 infection makes it difficult to differentiate, and one of the difficulties in the treatment of tuberculosis is the use of first-line drugs such as rifampicin. Note that there are potential side effects. Its DNA-dependent RNA polymerase inhibitor, which has been used for the treatment of tuberculosis for over 40 years, provides a broad spectrum of bactericidal activity against mycobacteria and many Gram-positive bacteria.

The authors of the cases indicate that although rifampicin-induced pneumonia is rare, the drug is associated with many other adverse effects, ranging from cutaneous reactions to fulminant liver or renal failure, in the setting of combination therapy with isoniazid. It has been widely studied in the treatment of tuberculosis.

The prevalence of drug-induced pneumonia depends on the drug used. Up to 50% of patients using methotrexate are reported to be affected, but the prevalence of noncytotoxic drugs is approximately 5-10%.

Given the importance of excluding other causes, antibiotic-induced pneumonia is commonly diagnosed after extensive workups such as radiographic imaging, bronchoscopy with lavage analysis, and biopsies.

The clinical, radiological, and histological findings of drug-induced pneumonia are comparable to those of ARDS, such as bronchoscopic ground-glass opacities. Early histological findings of ARDS include diffuse alveolar damage with an initial exudative phase followed by hyaline membrane formation.

Case authors note that drug-induced pneumonia features such as fever, cough, dyspnea, desaturation, and ground-glass opacities on CT scans of the chest are very similar to those of COVID-19 pneumonia. I point out. Maintain all recommended isolation precautions until COVID-19 is positively excluded.

Malignant tumors, allergic bronchopulmonary aspergillosis, autoimmune conditions (such as Churg-Strauss vasculitis, acute eosinophilic pneumonia, systemic lupus erythematosus), and all drug reactions to eosinophilia and systemic syndrome are pneumonia Differential diagnosis because it may exhibit the characteristics of.

Non-cytotoxic drug-related pneumonia-related risk factors include diabetes mellitus, decreased serum albumin levels, lung and pleural lesions due to rheumatoid arthritis, female sex, older age, and history of use of disease modifiers ..

As in this case, the symptoms of rifampicin-induced pneumonia generally include persistent low fever and shortness of breath with or without a cough. A diagnostic workup should begin with a chest x-ray. This may reveal interstitial infiltrates. Patients undergoing antibiotic/anti-tuberculosis therapy that remain negative despite testing negative for viral, bacterial, and mycobacterial pathogens should be evaluated further.

The author is 2002 Research In 60 patients with CT chest findings of antibiotic-induced pneumonia included speckled ground glass opacities with central opacification.

Other diagnostic tools that help distinguish drug-induced pneumonia from SARS-CoV-2 pneumonia include the following:

• Bronchoscopy, BAL analysis shows lymphocyte predominance results; SARS-CoV-2 RT-PCR from BAL Exclude COVID-19, Because of high sensitivity (sensitivity 93%)

• Tissue biopsy: Common findings include inflammatory cell infiltration, mild fibrosis, and uniform interstitial proliferation secondary to type II pulmonary hyperplasia

• Drug lymphocyte stimulation test. Diagnostic capacity is controversial, but sensitivity is 33% to 92% and rifampicin is low at 11.6%. A positive test suggests an immunological reaction, but negative results may be associated with false-negative results due to cytotoxic processes or immunocompromised secondary to steroid therapy

In pulmonary toxicity from drugs containing rifampicin, the first step is to discontinue the drug in question, the case authors stressed, and glucocorticoid therapy has shown excellent results and can be used in the absence of contraindications. I will add.

Conclusion

The team emphasizes the importance of early, rapid and accurate testing of this patient’s case for SARS-CoV-2, and the timely diagnosis of rifampicin-induced pneumonia to avoid permanent lung injury. He concludes that high clinical suspicion, detailed examination, and histopathological analysis are needed.

Last updated: August 31, 2020