“It’s Not Just Bacteria”: A Cavitary Lung Lesion in a Patient Living in the Coachella Valley

Abstract

Cavitary pulmonary coccidioidomycosis is rare diagnosis with an incidence of 13% to 15% of pulmonary coccidioidomycosis cases. High clinical suspicion is necessary in the setting of geographical location endemicity. We present a 49-year-old male who has lived in the Coachella Valley of California for several years, with a medical history of uncontrolled type 2 diabetes who noted 1 week of right-sided chest pain with shortness of breath, fever, chills, night sweats, and weight loss. A chest X-ray revealed a 4- to 5-cm mass in the right lung. Initial workup revealed negative sputum cultures (aerobic/anaerobic, acid-fast bacilli). However, dedicated fungal cultures (samples from sputum, lymph nodes, lung right lower lobe bronchial swabs), bronchial washings, and surgical tissue biopsy of the right lower lobe revealed mold. The patient underwent right thoracotomy with right lower lobectomy and right mediastinal lymph node dissection for both diagnostic (lung specimen) and therapeutic (removing necrotic lung tissue, source control) purposes. Finally, serum Coccidioides antigens were positive and antibody titers were positive at 1:8; surgical biopsy of the right lower lobe grew mold that came back positive for Coccidioides posadasii. Targeted pharmacotherapy was commenced using intravenous fluconazole and then oral fluconazole for 3 months was prescribed upon discharge. The patient had gradual improvement of his shortness of breath and was instructed to follow-up at an infectious disease clinic.

Introduction

Coccidioidomycosis is a fungal infection that is caused by the Coccidioides species including Coccidioides immitis and Coccidioides posadasii. ¹ Infections can be acquired through the inhalation route transmitted by the arthroconidia from soil. Coccidioidomycosis is endemic to desert areas of the southwestern United States, including California and Arizona, and Mexico. Symptoms of coccidioidal pneumonia include fever, headache, dry cough, shortness of breath, inspiratory chest pain, myalgia, and arthralgia, and may be accompanied by a rash. ¹ Most (around 60%) infections by Coccidoides organisms are asymptomatic; however, around 30% to 40% of infections by Coccidoides organisms manifest as a respiratory illness such as community-acquired pneumonia, in areas where the organism is highly prevalent. ² Extrapulmonary coccidioidomycosis can occur in sites such as skin, skeletal, or central nervous system.

We describe a patient who has lived in the Coachella Valley of California for several years, who was found to have a cavitary lung lesion that grew C posadasii. Cavitary pulmonary coccidioidomycosis is a rare presentation of the disease with an estimated incidence of 13% to 15% cases of pulmonary coccidioidomycosis cases. ³ Cavitary lung lesions can be caused by various microbes, including bacteria (Streptococcus pneumoniae, Staphylococcus aureus, Hemophilus influenzae, Klebsiella pneumoniae, Mycobacterium tuberculosis), fungi (Coccidioides, Rhizopus, Sporothrix schenckii), and parasites (Echinococcus granulosus). ⁴ The differential diagnosis of cavitary lung lesions broadly also includes infections, autoimmune conditions, and malignancies (both primary and metastatic). ⁵ In our patient, coccidioidomycosis likely led to necrotizing pneumonia and a right lower lobe cavitary lesion.

Case Summary

A 49-year-old male with a medical history of uncontrolled type 2 diabetes noted 1 week of right-sided chest pain with shortness of breath, fever (recorded febrile home temperature of 38.3 °C), chills, night sweats, and weight loss (5 pounds in the last 1 week). He had no history of chronic respiratory conditions including asthma, chronic obstructive pulmonary disease, or recurrent pneumonias. He also reported a progressive productive cough with dark green sputum since 2 months prior; he denied any generalized weakness or fatigue. He smoked since 16 years old, around three-fourths a pack per day, having switched to cigars around 10 years prior and is currently smoking 6 cigars daily. He used to work as a firefighter from age 16 to 21 years old with multiple exposures to fire-related smoke/fumes. He has lived in the Coachella Valley in Southern California for several years. He traveled to Arizona for a few days, 2 to 3 months prior. He also traveled to Mexico one time for a couple of days, several years prior. He had no travel history to countries in Asia. He had no recent dental procedures. He had no exposure to pets, farm animals, or other noxious fumes.

With other providers within the past 1 month, he underwent a chest X-ray and computed tomography (CT) chest, which both revealed a cavitary lung lesion. The patient had been taking oral amoxicillin-clavulanate for at least 1 week. The patient was then admitted for further evaluation.

On emergency room admission, the patient’s vitals were recorded as temperature 37^°C, heart rate 92 beats/min, respiratory rate 18 breaths/min, blood pressure 144/86 mmHg, SpO₂ 98% on room air. Labs were not significant for any gross electrolyte abnormalities. There was no anemia, leukopenia/leukocytosis, or thrombocytopenia/thrombocytosis. C-reactive peptide (CRP) was elevated at 11.3 mg/dL, random blood glucose was elevated at 445 mg/dL, and HbA1c was 13.7% (estimated average blood glucose 346 mg/dL). Procalcitonin levels were normal. Computed tomography chest from day 1 of admission (Figure 1) revealed an approximately 6-cm cavitary thick-walled lesion in the right lower lobe with numerous additional pericentimeter and subcentimeter micronodules elsewhere throughout the right lower lobe. He also had a small right pleural effusion; therefore, bedside ultrasound from day 1 of admission (Figure 2) was done which showed only minimal pleural effusion and there was no indication for thoracentesis.

Figure 1.

Computed tomography chest. Day 1 of admission. Of note, in the right lower lobe, there is an approximately 6-cm thick-walled, cavitating lesion with additional subcentimeter micronodules in the right lower lobe.

Figure 2.

Ultrasound. Day 1 of admission. There is a right-sided pleural effusion without loculations, not of adequate size/volume for thoracentesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by polymerase chain reaction (PCR) testing was negative on this admission, but the patient has previously tested positive for COVID 7 times with home SARS-CoV-2 antigen kits; the last positive test was 3 months prior to this admission. HIV-1 and HIV-2 antigen and antibody test was negative.

On day 1, the patient was started on broad spectrum antibacterial coverage with intravenous cefepime, intravenous metronidazole, and intravenous vancomycin. Intravenous vancomycin was stopped within the first 24 hours of admission after a PCR methicillin-resistant S aureus test of the nares was negative. Intravenous cefepime and metronidazole were stopped on day 2 of admission, and switched to intravenous piperacillin-tazobactam for concern of extended-spectrum beta-lactamase-producing K pneumoniae and oral doxycycline for atypical bacterial coverage.

On day 2, robotic bronchoscopy was performed. The airway peribronchial tissue showed gross black discoloration, consistent with anthracosis most likely associated with the patient’s previous history as a firefighter and associated smoke and fume exposure. ⁶ Samples taken from the right lower lobe included bronchial swabs, bronchial washings, and transbronchial tissue biopsies. Lymph nodes in stations 4L, 4R, 7, 11R superior, and 11R inferior were sampled via fine needle aspiration. Acid-fast bacilli testing was performed on samples from the right lower lobe transbronchial fine needle aspiration and biopsy, right lower lobe swab, lymph node biopsy, bronchial washing, pleural fluid, and sputum (induced, and from bronchoscopy).

Over days 3 to 5, the patient’s dyspnea (without hypoxemia) continued to worsen. A repeat CT chest scan (Figure 3) on day 5 of admission showed interval significant progression in multifocal right lower lobe pneumonia adjacent to stable-appearing right lower lobe thick-walled cavitary lesion. In addition, there was mild patchy ground glass opacifications in the right upper lobe, new from prior CT chest on day 1 of admission (Figure 1) with an increasing small right pleural effusion.

Figure 3.

CT chest axial (A) and sagittal (B) views. Day 5 of admission. There is significant progression in the multifocal right lower lobe pneumonia adjacent to an otherwise stable-appearing right lower lobe thick-walled cavitating lesion. There are also subtle mild patchy ground glass opacities in the right upper lobe, not seen on prior CT chest on day 1 of admission. There is also a small right pleural effusion.

Bronchial washings from the right lower lobe showed very rare growth of a mold on day 4 (day 5 of admission) of the culture (routine aerobic/anaerobic culture, not dedicated fungal culture). Therefore, on day 5, the patient was started on intravenous amphotericin B for broad spectrum empiric antifungal coverage.

On day 7, due to concern of spread of infection as demonstrated by increasing area of multifocal right lower lobe pneumonia, the patient underwent right thoracotomy with right lower lobectomy and right mediastinal lymph node dissection, for surgical biopsy diagnosis, debridement of necrotic tissue, and source control.

Fungal serologies, including Fungitell(R) (1-3)-B-D-Glucan assay, Aspergillus (flavus, niger, fumigatus species) immunodiffusion and enzyme immunoassay, Blastomyces antibody complement fixation and antibody immunodiffusion, Strongyloides antibody IgG, and Cryptococcus antigen, were negative. Autoimmune serology workup including myeloperoxidase antibody IgG, proteinase 3 antibody IgG, antinuclear antibody screen, rheumatoid factor was negative. Urine Legionella antigen enzyme immunoassay, S pneumoniae antigen, and Histoplasma galactomannan antigen were negative.

On day 10, the following results were positive: Coccidioides antibodies to TP antigen (IgM), antibody to F antigen (IgG) via immunodiffusion, and Coccidioides antibody complement fixation testing (titer of 1:8). On day 17, routine aerobic/anaerobic culture of the lung right lower lobe sample obtained via surgical biopsy confirmed fungal growth of C posadasii.

It was thought that Coccidioides fungal growth was the most likely etiology of the necrotizing multifocal pneumonia of the right lung, and right lower lobe cavitary lesion. Therefore, intravenous piperacillin-tazobactam was stopped on day 10. Oral doxycycline was stopped on day 5. Intravenous amphotericin B was stopped on day 9. Targeted antifungal therapy was commenced with intravenous fluconazole 400 mg daily started on day 10 until discharge (day 18). On discharge, the patient was instructed to continue oral fluconazole 400 mg daily for at least 3 months and instructed to follow-up at the specialist infectious disease clinic.

Discussion

In light of the patient’s worsening dyspnea, worsening radiological findings, routine aerobic/anaerobic sputum cultures and bronchial washings both showing rare growth of a mold, a diagnosis of fungal infection, particularly cavitary coccidioidomycosis, was considered. For coccidioidomycosis, the only suspicion was the patient’s geographic location of desert; the patient did not have other exam findings such as skin lesions (eg, erythema nodosum) indicative of another rheumatological disorder. Given the concern for potentially rapid progression, the patient underwent surgical biopsy, debridement, and source control by the cardiothoracic surgery team.

Later, as the fungus was identified on surgical lung tissue biopsy as C posadasii, there were questions raised whether surgical consult and intervention early on was of high importance. Cardiothoracic surgery intervention was critical here. Notably, the surgical lung tissue biopsy was the first definitive identification of C posadasii on day 17. While the serum Coccidioides antibodies were positive on day 10 but did not identify a specific Coccidioides species, it is notable that our institution’s lab requires this test to be sent out to an external lab, increasing the delay in diagnosis. In addition, cavitary pulmonary coccidioidomycosis is difficult to diagnose in patients, with poor test sensitivity overall. In one study, only 48% of patients in a 21-patient study had positive serology to indicate Coccidioides infection. ³ While our patient did have both positive Coccidioides serology and identification through surgical lung tissue biopsy, there were clear indications for urgent surgical intervention: (1) the rapidity with which other lobes of the lung were getting involved and (2) the lack of penetration of antifungal agents into the necrotic tissue.

Although conventional approaches to diagnosing coccidioidomycosis involve detection of specific anti-coccidioidal antibodies and/or identification or recovery of Coccidioides spp. from clinical specimens, the diagnosis of coccidioidomycosis requires a high index of suspicion and consideration for this infection. ⁷ Establishing the diagnosis of pulmonary coccidioidomycosis is vital to avoid antibiotic courses, providing the patient a specific diagnosis, enabling education, and ensuring appropriate follow-up for complications or disseminated disease. Confirmatory diagnosis proves even more challenging when clinicians realize that pulmonary coccidioidomycosis often presents like a classic bacterial pneumonia which has a very different treatment algorithm; thus, when the patient has risk factors (eg, the patient lives in an endemic area), suspicion must be high to begin a pathway to accurate diagnosis and correct management. ⁸ Notably, due to delay in confirmation of the diagnosis, our patient received nephrotoxic antibiotics and imaging with contrast which cause acute kidney injury.

Elevated serum CRP is a common laboratory finding in patients with community-acquired pneumonia, including those with pulmonary coccidioidomycosis. ⁹ However, serum white blood cell counts are often normal, and the differential may show eosinophilia but it is often not seen. ⁹ Serum (1→3)-β-d-glucan (BG) can be used to identify invasive fungal infections involving species such as Candida and Aspergillus. However, in acute pulmonary coccidioidomycosis, the BG test has a 19% sensitivity; so in the case of a negative BG result in acute pulmonary coccidioidomycosis, the disease is not ruled out. ¹⁰

Finally, it is vital to distinguish cavitary pulmonary coccidioidomycosis from conditions which mimic cavities such as cysts, cystic bronchiectasis, and infected bullae and emphysema. Imaging including but not limited to CT scanning is useful for influencing management. ¹¹ Also, chronic cavitary pulmonary coccidioidomycosis is commonly seen in old and immunocompromised patients ¹² such as our patient with suboptimally controlled diabetes. Thus, in addition to the antifungal therapy for at least 3 months, one must address the root cause with appropriate comorbidity management (eg, diabetes).