In this report, we describe a 28-year-old Saudi man who was previously healthy. His medical history dates back to January 2020, when he had a 40-day dry cough, fever, fatigue, and red eyes, as well as abnormal chest x-rays. He smoked 10 packs a year. In August 2019, he underwent a lumbar laminectomy for left sciatica. Prior to admission, he had dry cough, red eyes, blurred vision, arthralgia in both knees, and low back pain. His chest X-ray showed an isolated pulmonary nodule in the right upper lobe, so he was referred to the pulmonary clinic (Figure 1A).
Since pulmonary tuberculosis is common in our area, we performed outpatient tuberculosis screening by sputum analysis for acid fast bacteria by smear and PCR. The result of the test was negative. A second chest X-ray 2 weeks later revealed bilateral pulmonary nodules, the largest in the right upper lobe.
He was admitted to another hospital, where an examination and flexible bronchoscopy with transbronchial biopsy of the right upper lobe was performed, which revealed no endoluminal lesion.
He denied fever, rash, numbness, headache, joint swelling, nasal congestion or discharge, or change in urine color. His examination revealed a body mass index of 30.5 kg/m2, a temperature of 37.0*C, a blood pressure of 130/80 mmHg, a heart rate of 110 beats per minute, and an oxygen saturation of 95%. His eyes were red bilaterally, without discharge. We found no nasal polyps or deformities. The chest was auscultated bilaterally with equal air entry. His abdomen was neither tender nor distended and there was no evidence of organomegaly. The patient had no accessible lymphadenopathy, rash, or arthritis. An ophthalmologist noted bilateral episcleritis.
Subsequent chest radiographs showed: enlargement of the right upper lobe nodule with formation of a cavitary massive opacity and enlargement of the left lower lobe nodule (Figure 1B).
An imaging examination on February 10, 2020 revealed multiple nodules of varying sizes on both sides of the chest and an enlarged lung mass in the right upper lobe with multiple mediastinal lymph nodes (Figure 2A and B). Infectious etiologies included bacterial infections, tuberculosis, and even mycoses. Sarcoidosis and granulomatosis with polyangiitis are other differential diagnoses. The possibility of a neoplastic process also cannot be ruled out. His investigations revealed microscopic haematuria and proteinuria and mild eosinophilia in the blood (Table 1). 
He was admitted to our hospital on February 15, 2020, and a CT -guided lung biopsy was performed under local anesthesia without complications from the cavitary lesion of the right upper lobe (Figure 2C and D). In addition to intravenous steroids (methylprednisolone 1), we started ambulatory steroids (prednisolone 50 mg daily) and methotrexate 25 mg every other week for five days.
Histopathology of the cavitary lesion of the right upper lobe revealed the following: The medium-sized vessels (arteries and veins) are typically absent due to inflammation and are replaced by scattered necrosis containing karyorrhectic neutrophils and eosinophils with fibrinoid necrosis (probable foci of leukocytoclastic vasculitis). The lesion consists of epithelioid-granulomatous collections of granulomas with occasional central small necrosis and multinucleated giant Langerhans cells. An overlap syndrome between GPA and eosinophilic granulomatosis with polyangiitis has been reported in the literature. Eosinophilic granulomatosis with polyangiitis was ruled out in this case based on the clinical history (no asthma, no atopy, and no significant peripheral eosinophilia) (Figure 3A and B).
His immunological profile showed positive results for antineutrophil cytoplasmic antibody (ANCA) C, rheumatoid factor, but negative results for p-ANCA, antinuclear antibody (ANA) and anticyclic citrullinated antibody (CCA). As he has no children and is single, he refused cyclophosphamide.
He received a bolus of intravenous (IV) methylprednisolone three times a month for 3 months and oral prednisolone 50 mg in combination with methotrexate 25 mg once a week and sometimes mycophenolate mofetil (2 grams daily). After 3 months, his condition still had not improved clinically and radiologically, so rituximab 2 grams IV 500 mg was given every 2 weeks for 4 doses, but he developed a severe allergic reaction after the fourth dose.
On September 17, 2020, in addition to fever, he developed increased cough, yellowish, sometimes bloody sputum, fatigue, and shortness of breath. He developed arthralgia and his eyes became red again. Clinically, he had a temperature of 39 C, a pulse of 140 beats per minute, and a respiratory rate of 28 beats per minute. Eyes were red, no lower limb edema, no rash, no arthritis Heart murmur was normal with no murmur. Dullness in the chest over both bases and distant air entry. A repeat chest x-ray showed progression of dimensions of multiple cavities with air-fluid levels (Figure 1C). Blood and sputum cultures were negative for bacteria, but sputum cultures were positive for Aspergillus on 3 occasions. On many occasions, the serum galactomannan test was negative. His inflammatory markers were elevated, and COVID -19 was repeatedly negative. He was recently diagnosed with type 2 diabetes and was taking basal and normal insulin. Empirically, an intravenous antibiotic was initiated, but after the result of a culture, voriconazole 200 mg/8 hours was administered intravenously for two weeks, followed by an oral dose.
During treatment, prednisolone 20 mg daily and voriconazole 200 mg thrice daily were given along with azathioprine 100 mg pod daily and trimethoprim and sulfamethoxazole 480 mg daily. He had purulent manifestations (cough and sputum with excessive sputum and fever, myalgia and fatigue with elevated inflammatory markers with negative sputum and blood cultures. Multiple courses of IV broad spectrum antibiotics were administered, each lasting three weeks, both inpatient and outpatient.
In March 2021, he was clinically stable with partial radiological improvement.
He developed bilateral cataracts and a bilateral catarcetomy was performed on 2 occasions under local anesthesia.
In June 2021, he developed an episode of purulent manifestations (cough and excessive sputum) with fever, myalgia and fatigue with an increase in inflammatory markers with negative sputum and blood cultures. Fungal culture in sputum was positive for Aspergillus fumigatus. Intravenous cyclophosphamide 500 mg monthly for 3 months with intravenous amphotericin b (Ambisome) 200 mg daily for 12 weeks. He began to become asymptomatic and improved clinically, radiologically, and laboratory. The oral steroid was reduced to 10 mg prednisolone daily. With trimethoprim and prophylaxis for gastritis and osteoporosis.
After 12 weeks of treatment with IV Ambisome and restarting oral voriconazole (200 mg three times daily) without sufficient response, he was admitted to King Faisal Special Hospital in Riyadh and evaluated in July 2021 by flexible bronchoscope (BAL) and CT guided lung biopsy of the left lower lobe. BALF was negative for malignancy, viruses and fungi (by staining) but positive for galactomannan (8,3). Serum galactomannan was negative (0.09).
The cardiothoracic surgeon, pulmonary rheumatology, and infectious disease team recommended continuing drug treatment for the fungal infection, as the patient had multiple lung cavity lesions, some of which had air fluid (active infection?), and reducing the oral corticosteroid to 10 mg daily. Lung biopsy revealed nonspecific inflammation.
Follow-up CT on October 1, 2021 showed that the bilateral cavitary lung lesions had decreased in size and had markedly increased wall thickening (Figure 2E and F).
On October 26, 2021, he was reexamined at King Faisal Specialized Center by a multidisciplinary team. It was recommended to continue medical treatment and perform surgical intervention after ponding until the fungal infection is under control or complications occur.