CHEST 2024

Undercover Coccidioidomycosis: A Cryptic Case Presentation of Pulmonary Coccidioides Infection in an Immunocompromised Patient

Introduction

• 1. Coccidioidomycosis is an infection by the dimorphic fungus, Coccidioides immitis, characterized by the following:
  • a. Endemic to the soils of the southwestern United States and South America
  • b. Spreads through the inhalation of its aerosolized spores
  • c. Mainly asymptomatic in healthy individuals
  • d. Risk of life-threatening dissemination, with symptoms including fever, arthralgias, erythema nodosum, and chest pain
• 2. Diagnosis is difficult since it relies on clinical suspicion despite nonspecific symptoms
• 3. A delayed diagnosis can result in adverse patient outcomes due to lack of treatment, with a higher risk in the immunocompromised

We present the case of a 74-year-old woman who followed up with her pulmonologist after a recent ER visit for upper respiratory infection symptoms.

The immunocompromised patient has a past medical history of pulmonary arterial hypertension for eight years, COPD for five years, and cirrhosis for five years.

Case Presentation

Initial presentation...

• 1. Dry cough and wheezing for a couple weeks
• 2. Unremarkable physical exam
• 3. Chest x-ray from the ER visit showed:
  • a. Right pleural effusion
  • b. Bibasilar R > L atelectasis or airspace
  • c. Concerns for pneumonia

Two weeks later...

• 1. No improvement despite two rounds of levofloxacin
• 2. Positive for recent weight loss and poor appetite
• 3. Proceeded with a full workup including another chest x-ray, bronchoscopy with BAL and biopsy, and AFB smear
  • a. Negative for malignancy
  • b. Negative AFB smear
  • c. Negative viral cultures
  • d. Positive for acute inflammation

By two months following her initial presentation...

• 1. BAL was positive for two species:
  • a. First, result of contamination with Penicillium
  • b. Later, result of Coccidioides immitis
• 2. Initiated treatment with 200 mg of fluconazole twice daily

Discussion

• 1. Symptomatic coccidioidomycosis will typically present as a primary lung infection similar to a community-acquired pneumonia
  • a. Especially with co-existence of other pulmonary comorbidities and without specific identifiers, diagnosis is difficult and delayed
• 2. Around two-thirds of patients infected were misdiagnosed prior to the discovery of the fungal infection
• 3. Treatment is supportive and does not require pharmacological intervention
  • a. However, antifungal treatment is indicated for the immunocompromised due to the increased risk for disseminated disease

Conclusions

• 1. Majority of current literature focuses on how to manage symptomatic coccidioidomycosis presenting with the classic clinical symptoms
• 2. We highlight the importance of an individualized approach and avoiding delayed diagnosis, especially in the immunocompromised patient with multimorbidity

References

• 1. Reference #1: Hernandez, H., Erives, V.H. & Martinez, L.R. Coccidioidomycosis: Epidemiology, Fungal Pathogenesis, and Therapeutic Development. Curr Trop Med Rep 6, 132–144 (2019). https://doi.org/10.1007/s40475-019- 00184-z
• 2. Reference #2: Williams SL, Chiller T. Update on the Epidemiology, Diagnosis, and Treatment of Coccidioidomycosis. Journal of Fungi. 2022; 8(7):666. https://doi.org/10.3390/jof8070666

Pulmonary Manifestations of Systemic Disease

• Session Title: Pulmonary Manifestations Case Reports Posters (I)
• Session Type: Case Report Posters

Pulmonary Lymphomatoid Granulomatosis: Delayed Diagnosis and The Dilemma of Loss to Follow-up

Introduction

Lymphomatoid Granulomatosis (LYG) is a rare lymphoproliferative Epstein-Barr virus-associated disease that presents as lymphocytic invasion, in the form of multiple nodular lesions in the vascular walls of the lungs - an angiocentric proliferative disease comprised of sites that involve abnormal B-cell lymphocytes positive for EBV. Patients diagnosed with LYG primarily present with a deficient immune system, resulting in challenges of concrete treatment and daily life to compound. This case report highlights a patient's complicated history of evaluation before being diagnosed with LYG.

Case Presentation

We present a 51-year-old female with a history of COPD, hypothyroidism, sacral pressure injury, and nicotine dependence with a 15 packyear history. She endorsed coughing, wheezing, and dyspnea on exertion and denied chest discomfort, fever, chills, hemoptysis, and unintentional weight loss. Physical exam was unremarkable, and the patient was underweight (BMI of 15.7). The screening CT demonstrated multiple peripheral, confluent areas of opacity at the lung apices and throughout the bilateral upper lobes. The largest nodule measured 3.1 x 2.3 cm. The patient underwent an ION robotic bronchoscopy with transbronchial lung biopsy, fine needle aspiration (FNA), and brushings with endobronchial ultrasound which was delayed 4 months from the time of initial screening. The preop CT revealed no perceivable changes to the imaging during that time. Thorough chart review following this observation revealed that the patient's lung nodules have had a grossly stable distribution since 2018. In 2020 the patient presented to the ER with vomiting, dyspnea, productive cough, fever, and 30-40 lbs. of unintentional weight loss. A Chest CT demonstrated extensive, large masslike infiltrates ranging in size from 3-5cm scattered throughout with a subcentimeter nodule at the left lung base. Blood and Sputum cultures were gathered yielding negative AFB and mycobacterium cultures. Tough TB QuantiFERON Gold was positive, Infectious Disease consult did not suspect tuberculosis. CT-guided FNA of the right upper lung was unremarkable for malignancy and significant for chronic inflammation, interstitial fibrosis, and focal fibrin deposition. Similar to the 2020 biopsy result, the pathology report following the patient's biopsy in December of 2023 was negative for malignancy. The samples showed atypical lymphoid infiltrate showing immunoreactivity for CD20 in 80% of lesional lymphocytes with CD3 cells accounting for the remainder. In-situ hybridization (ISH) preparations for Epstein-Barr encoding region (EBER) yielded negative results. However, serum EBV viral capsid antigen IgG antibodies measured 311, and EBV nuclear antigen antibodies measured >600.

Discussion

Despite ISH for EBER being negative, the atypical B cells found in the biopsy, clinical picture, and radiological findings were consistent with LYG. The patient's lack of treatment and repeated loss to follow-up is significant in that her disease state has remained stable. Considering LYG is often associated with rapid progression and a poor prognosis, our patient's presentation and stable imaging may suggest spontaneous remission.

Conclusions

Lymphomatoid Granulomatosis should be included in a broad differential in the evaluation of multipulmonary nodule pathology. This case highlights the importance of follow-up for definitive and timely diagnosis.

References

REFERENCE #1: 1. Nazir A Lone, and Ploypin Lertjitbanjong. "Lymphomatoid Granulomatosis: Background, Pathophysiology, Epidemiology." EMedicine, 9 Jan. 2024, emedicine.medscape.com/article/299751-overview. Accessed 14 Mar. 2024.
2. Roschewski, Mark, and Wyndham H. Wilson. "Lymphomatoid Granulomatosis." The Cancer Journal, vol. 18, no. 5, Sept. 2012, pp. 469–474, https://doi.org/10.1097/ppo.0b013e31826c5e19. Accessed 27 Mar. 2022.

REFERENCE #2: 3. Elaine S. Jaffe, et al. "Lymphomatoid Granulomatosis - Symptoms, Causes, Treatment | NORD."Rarediseases.org, 20 Mar. 2020, rarediseases.org/rare-diseases/lymphomatoid-granulomatosis/.
4. Talmadge E King, Jr, MD. "UpToDate." Www.uptodate.com, 27 Nov. 2023, www.uptodate.com/contents/pulmonary-lymphomatoid-granulomatosis. Accessed 14 Mar. 2024.

REFERENCE #3: 5. "Immunotherapy Effective for Lymphomatoid Granulomatosis - NCI." Www.cancer.gov, 4 Apr. 2023, www.cancer.gov/news-events/press-releases/2023/immunotherapy-lymphomatoid-granulomatosis. Accessed 14 Mar. 2024.
6. Dr chestjournal.org 5453A PULMONARY MANIFESTATIONS OF SYSTEMIC DISEASE Ritva Vyas. "Lymphomatoid Granulomatosis | DermNet." Dermnetnz.org, dermnetnz.org/topics/lymphomatoid-granulomatosis. Accessed 14 Mar. 2024.

Pulmonary Lymphomatoid Granulomatosis: Delayed Diagnosis and the Dilemma of Loss to Follow-Up

Case Presentation

We present a 51-year-old female with a history of COPD and nicotine dependence with a 15 packyear history. She endorsed coughing, wheezing, and dyspnea on exertion and denied chest discomfort, fever, chills, hemoptysis, and unintentional weight loss. Physical exam was unremarkable, and the patient was underweight (BMI of 15.7).

The screening CT demonstrated multiple peripheral, confluent areas of opacity at the lung apices and throughout the bilateral upper lobes. The largest nodule measured 3.1 x 2.3 cm.

The patient underwent an ION robotic bronchoscopy with transbronchial lung biopsy, fine needle aspiration (FNA), and brushings with endobronchial ultrasound which was delayed 4 months from the time of initial screening. The preop CT revealed no perceivable changes to the imaging during that time. Thorough chart review following this observation revealed that the patient’s lung nodules have had a grossly stable distribution since 2018.

In 2020 the patient presented to the ER with vomiting, dyspnea, productive cough, fever, and 30-40 lbs. of unintentional weight loss. A Chest CT demonstrated extensive, large masslike infiltrates ranging in size from 3-5cm scattered throughout with a subcentimeter nodule at the left lung base.

Blood and Sputum cultures were gathered yielding negative AFB and mycobacterium cultures. Though TB QuantiFERON Gold was positive, Infectious Disease consult did not suspect tuberculosis. CT-guided FNA of the right upper lung was unremarkable for malignancy and significant for chronic inflammation, interstitial fibrosis, and focal fibrin deposition.

Like the 2020 biopsy result, the pathology report following the patient’s biopsy in December of 2023 was negative for malignancy. The samples showed atypical lymphoid infiltrate showing immunoreactivity for CD20 in 80% of lesional lymphocytes with CD3 cells accounting for the remainder. In-situ hybridization (ISH) preparations for Epstein-Barr encoding region (EBER) yielded negative results. However, serum EBV viral capsid antigen IgG antibodies measured 311, and EBV nuclear antigen antibodies measured >600.

Discussion

Despite ISH for EBER being negative, the atypical B cells found in the biopsy, clinical picture, and radiological findings were consistent with LYG. The patient’s lack of treatment and repeated loss to follow-up is significant in that her disease state has remained stable. Considering LYG is often associated with rapid progression and a poor prognosis, our patient’s presentation and stable imaging may suggest spontaneous remission.

Conclusion

Lymphomatoid Granulomatosis (LYG) is a rare lymphoproliferative Epstein-Barr virus-associated disease that presents as lymphocytic invasion, in the form of multiple nodular lesions in the vascular walls of the lungs - an angiocentric proliferative disease comprised of sites that involve abnormal B-cell lymphocytes positive for EBV. Patients diagnosed with LYG primarily present with a deficient immune system, resulting in challenges of concrete treatment and daily life to compound.

Lymphomatoid Granulomatosis should be included in a broad differential in the evaluation of multi-pulmonary nodule pathology. This case highlights the importance of follow-up for definitive and timely diagnosis.

References

1. 1. Nazir A Lone, and Ploypin Lertjitbanjong. "Lymphomatoid Granulomatosis: Background, Pathophysiology, Epidemiology." EMedicine, 9 Jan. 2024, emedicine.medscape.com/article/299751-overview. Accessed 14 Mar. 2024.
2. 2. Roschewski, Mark, and Wyndham H. Wilson. "Lymphomatoid Granulomatosis." The Cancer Journal, vol. 18, no. 5, Sept. 2012, pp. 469–474, https://doi.org/10.1097/ppo.0b013e31826c5e19. Accessed 27 Mar. 2022.
3. 3. Elaine S. Jaffe, et al. "Lymphomatoid Granulomatosis - Symptoms, Causes, Treatment | NORD." Rarediseases.org, 20 Mar. 2020, rarediseases.org/rare-diseases/lymphomatoid-granulomatosis/.
4. 4. Talmadge E King, Jr, MD. "UpToDate." Www.uptodate.com, 27 Nov. 2023, www.uptodate.com/contents/pulmonary-lymphomatoid-granulomatosis. Accessed 14 Mar. 2024.
5. 5. "Immunotherapy Effective for Lymphomatoid Granulomatosis - NCI." Www.cancer.gov, 4 Apr. 2023, www.cancer.gov/news-events/press-releases/2023/immunotherapy-lymphomatoid-granulomatosis. Accessed 14 Mar. 2024.
6. 6. Dr Ritva Vyas. "Lymphomatoid Granulomatosis | DermNet." Dermnetnz.org, dermnetnz.org/topics/lymphomatoid-granulomatosis. Accessed 14 Mar. 2024.