First Report of Splenic Abscesses Due to Coccidioidomycosis

Shabnam Assar, MD^I and Tim Kuberski, MD, FIDSA²

¹Department of Medicine, Virginia Tech Carilion, Roanoke, Virginia USA

²Department of Medicine, University of Arizona School of Medicine-Phoenix,

Phoenix, Arizona USA

Abstract

Involvement of the spleen by Coccidioides is uncommon. It is usually associated only with disseminated infection and manifests as microscopic granulomas in the spleen. We report an immunosuppressed dermatomyositis patient who presented with splenic abscesses demonstrated on a computed tomography (CT) scan which was presumed to be bacterial in origin. At splenectomy the spleen was found to be filled with aggregates of spherules due to Coccidioides. Finding large splenic abscesses on CT scan due to Coccidioides has not been previously described. We offer a hypothesis for why the abscesses occurred in this unique patient.

Introduction

Involvement of the spleen by coccidioidomycosis is usually associated with disseminated disease, however the development of splenic abscesses has not been reported. Splenic involvement by coccidioidomycosis is usually manifest as microscopic miliary splenic granulomas which have been demonstrated at autopsy in patients with disseminated infection (1,2). We report an immunocompromised dermatomyositis patient who was found to have splenic abscesses due to Coccidioides spherules which were diagnosed at splenectomy.

Case Presentation

A 33-year-old Hispanic man with dermatomyositis for five years and a history of disseminated coccidioidomycosis for two years, presented to the emergency room because of left upper quadrant abdominal pain, fever and chills. Treatment of his dermatomyositis was ongoing over the previous five years and included prednisone, azathioprine and courses of intravenous immunoglobulin (IVIG) at doses of 2 g/kg (3). Treatments of his coccidioidomycosis over the previous two years included intravenous liposomal amphotericin B followed by oral fluconazole. The patient would periodically be non-compliant about taking the fluconazole and then experience relapses of his coccidioidomycosis which required additional courses of intravenous liposomal amphotericin B.

Physical Examination and Course: Admission vital signs - temperature 38.4⁰ C; blood pressure 147/81 mmHg; heart rate 106 bpm; respiratory rate 18 breaths/minute and pulse oximetry 90% on room air. There was pigmentation of his face consistent with dermatomyositis, tenderness in the left upper quadrant and significant weakness of all extremities. He was bedridden and could barely move his arms and legs against gravity. His medications on admission were fluconazole and prednisone. An admission CT scan of the abdomen was performed because of the left upper quadrant tenderness and revealed multiple splenic abscesses (Figure 1).

Figure 1. CT scan of abdomen demonstrating splenic abscesses (arrow).

An admission urine culture grew >10⁵ colony forming Klebsiella pneumoniae which was noted on day two of hospitalization. Blood cultures were negative. It was initially believed that the splenic abscesses were due to a Klebsiella infection because of the admitting urine culture results. Prednisone was stopped on admission and the oral fluconazole continued. Piperacillin-tazobactam was started empirically on admission. In addition, IVIG was given for a presumed dermatomyositis exacerbation. On hospital day four his abdominal pain and fevers had not improved. To avoid a splenectomy, a splenic biopsy was performed to determine the cause of the splenic abnormalities. The biopsy was consistent with a Coccidioides infection. A laparoscopic splenectomy was then preformed on hospital day seven.

The pathology on the removed spleen showed multiple necrotizing granulomatous foci containing numerous aggregated Coccidioides spherules (Figure 2).

Figure 2. Pathology of splenic abscesses demonstrating aggregated Coccidioides spherules.

Post-operatively, fluconazole was empirically replaced by voriconazole (4) and the patient was restarted on prednisone for his dermatomyositis. The fever and chills eventually resolved and he was discharged. At four months follow-up he had returned to his usual state and was encouraged to not stop taking the voriconazole.

Discussion 

This patient illustrates an unusual complication of disseminated coccidioidomycosis. Prior to the advent of CT scans, splenic granulomas were described mainly at autopsy in patients with disseminated infection. Splenic involvement at autopsy was described as granulomas due to the invasion of the Coccidioides into the spleen from the blood stream. Usually there was granuloma formation described as microscopic military nodules. Reports of gross Coccidioides abscesses in the spleen have not been described.

We considered the potential reasons for the development of splenic abscesses in this unique patient. His dermatomyositis was present for about five years and the coccidioidomycosis, two years. He had received repeated doses of IVIG for flares of his dermatomyositis prior to, and after, his Coccidioides infection. Investigating his past medical history revealed that he would develop a febrile illness when off fluconazole - usually due to non-compliance. The clinical presentation was consistent with either a relapse of his Coccidioides infection, an exacerbation of his dermatomyositis, or both. The febrile episodes would cause him to be admitted to the hospital, often into the intensive care unit, and then he would receive more IVIG for his dermatomyositis, as well as antifungals. It is known that fungemia occurs in immunosuppressed patients who have significant coccidioidomycosis (5). The fact that he had a large Coccidioides burden in his spleen suggests he likely experienced episodes of fungemia, presumably associated with his poor antifungal compliance.

Our hypothesis for why the abscesses formed in the spleen of this patient is illustrated in Figure 3.

Figure 3. Hypothesis of Coccidioides abscess formation in the spleen.

We theorized that Coccidioides endospores in the blood stream became coated with the gamma globulins when he received the IVIG given for his dermatomyositis (6).  The opsonization of the organisms by the IVIG presumably facilitated the spleen to take up viable endospores into the spleen and reticuloendothelial system (Figure 3, part 3). This resulted in the localization of the organisms promoting the formation of an abscess within the spleen (Figure 3, part 4). We suggest that these unusual circumstances of fungemia and IVIG were responsible for facilitating the appearance of abscesses in this patient's spleen.

We believe true splenic abscesses are uncommon with disseminated coccidioidomycosis. The unusual circumstances of this patient's relapsing Coccidioides infection with fungemia (due to poor compliance with antifungals) and the repeated IVIG treatments for his dermatomyositis, combined to provide a reasonable explanation for why splenic abscesses occurred in this patient.

References

1. Forbus WD, Bestebreurtje AM. Coccidioidomycosis; a study of 95 cases of the disseminated type with special reference to the pathogenesis of the disease. Mil Surg. 1946 Nov;99(5):653-719. [PubMed]
2. Fiese MJ. Coccidioidomycosis: Springfield, IL: Charles C. Thomas 1958; p 111.
3. Wang DX, Shu XM, Tian XL, Chen F, Zu N, Ma L, Wang GC. Intravenous immunoglobulin therapy in adult patients with polymyositis/dermatomyositis: a systematic literature review. Clin Rheumatol. 2012 May;31(5):801-6. [CrossRef] [PubMed]
4. Prabhu RM, Bonnell M, Currier BL, Orenstein R. Successful treatment of disseminated nonmeningeal coccidioidomycosis with voriconazole. Clin Infect Dis. 2004 Oct 1;39(7):e74-7. [CrossRef] [PubMed]
5. Rempe S, Sachdev MS, Bhakta R, Pineda-Roman M, Vaz A, Carlson RW. Coccidioides immitis fungemia: clinical features and survival in 33 adult patients. Heart Lung. 2007 Jan-Feb;36(1):64-71. [CrossRef] [PubMed]
6. Adkinson NF, Yunginger JW, Busse WW, et al. Middleton's Allergy Principles & Practice (6th ed) Philadelphia, PA: Mosby, 203; 72-73.

Cite as: Assar S, Kuberski T. First report of splenic abscesses due to coccidioidomycosis. Southwest J Pulm Crit Care. 2017;15(5):214-8. doi: https://doi.org/10.13175/swjpcc125-17 PDF 

November 2017 Pulmonary Case of the Month

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 67-year-old man developed a right neck mass and underwent a right radical neck dissection. It was initially thought to be a high-grade sarcomatoid cancer, but after review was determined to be metastatic melanoma.

Past Medical History, Social History and Family History

He had no significant past medical or family history. He was a nonsmoker.

Physical Examination

His initial physical examination showed a right neck mass but was otherwise unremarkable. No abnormal skin lesions were identified.

PET/CT Scan

A positron emission tomography/computed tomography (PET/CT) scan showed increase uptake in the neck (Figure 1A) but his chest showed no increased uptake (Figure 1B).

Figure 1. Panel A: PET/CT scan showing increased tracer uptake in the right neck (arrow). Panel B: No abnormal tracer uptake is seen within the chest.

Which of the following is/are true? (Click on the correct answer to proceed to the second of four pages)

1. Bronchoscopy should be performed to search for bronchial melanoma
2. Radiation and oncology consultation should be obtained
3. The pathologic diagnosis is likely wrong since no primary melanoma can be identified
4. 1 and 3
5. All of the above

 Cite as: Wesselius LJ. November 2017 pulmonary case of the month. Southwest J Pulm Crit Care. 2017;15(5):181-7. doi: https://doi.org/10.13175/swjpcc117-17 PDF 

Treatment of Lymphoma and Cardiac Monitoring during Pregnancy

Stella Pak, MD

Yan Yatsynovich, MD 

Damian Valencia, MD

Calvert Busch, MD

Emily Vannorsdall, MD

Department of Medicine

Kettering Medical Center

Kettering, OH USA

Abstract

Limited data is available regarding fetal-maternal outcomes with chemotherapy during pregnancy, including cardiovascular toxicity and evaluation thereof. Early cardiovascular evaluation and initiation of cardioprotective therapies should be considered. Herein, we report a case of a 33-year-old woman treated with R-CHOP chemotherapy for large B-cell lymphoma found to have some degree of reversible cardiac strain.

Introduction

There are no guidelines specific for cardiotoxicity monitoring in pregnant patients undergoing chemotherapy. Pregnant patients are more vulnerable to cardiovascular complications, such as congestive heart failure, from chemotherapy as their cardiovascular system is under considerable stress from increasing physiological demands in pregnancy. With elevated cardiac output and circulatory volume from baseline, these patients do not have much cardiopulmonary reserve to compensate for cardiac strains from chemotherapy side effects (1). Therefore, it would be critical for clinicians to be aware of increased risk of cardiovascular adverse effect from chemotherapeutic agents in pregnant patients. Herein, we report a case of a 33-year-old woman treated with R-CHOP chemotherapy for large B-cell lymphoma found to have some degree of reversible cardiac strain.

Case Presentation

An otherwise healthy 33-year-old Caucasian female, G2P1 at 24 weeks gestation presented with a chief complaint of cough, chest pressure, and swelling in the neck and face. Physical exam was notable for a negative Pemberton’s sign, two lymph nodes in the right supraclavicular region measuring approximately 2 cm without axillary or groin lymphadenopathy. Cardiac exam demonstrated distant heart sounds with a faint I-II/VI systolic murmur in the left second intercostal space, without presence of bruits or lower extremity edema. Lung exam was positive for occasional wheezing in the left lower lobe. Breast exam was normal. Initial chest x-ray (Figure 1) and computed tomography (CT) scan (Figure 2) of the chest revealed a mediastinal mass (11 x 9.2 x 8.7 cm) and a moderate sized pericardial effusion.

Figure 1. Roentgenogram of chest demonstrating a large mass on left lower lobe and pericardial effusion.

Figure 2. Computerized tomography of chest revealing a large homogeneous left mediastinal mass (92.1 mm X 87.1 mm).

Follow up CT-guided biopsy yielded a diagnosis of large B-cell lymphoma. Bronchoscopy done at that time demonstrated diffuse tracheal and bronchial involvement, likely pointing to primary mediastinal derivation of the tumor. Interestingly, the patient had a history of lymph node biopsy of two areas on her right lateral neck and right medial supraclavicular node; pathology reports were consistent with granulomatous disease at that time. Due to pregnancy, baseline positron emission tomography (PET)/CT was not performed, however, the patient did undergo staging with a CT scan of the chest and abdominal/pelvic and magnetic resonance imaging (MRI), both of which were negative for metastatic disease. Bone marrow biopsy obtained was negative for malignancy as well. Dose-adjusted R-EPOCH (rituximab, etoposide, prednisone, oncovin, cyclophosphamide, hydroxydaunorubicin) was replaced with R-CHOP (rituximab, cyclophosphamide, hydroxydaunomycin, oncovin, prednisolone) due to the teratogenic effects of etoposide. Embryologic toxicity has previously been observed with etoposide including skeletal abnormalities, exencephaly, encephalocele and anophthalmia. Monitoring of cardiac function was performed before, during and after treatment. Initial echocardiogram demonstrated preserved ejection fraction (EF) of 60% with a large pericardial effusion and early signs of tamponade. No strain studies were done prior to initiation of chemotherapy. The patient had undergone a total of six cycles with a good response. Upon treatment completion fluoro-D-glucose (FDG)-PET/CT did show persistent uptake mostly in the manubrium as well as a persistent mediastinal mass with a low standardized uptake values (SUV).

The patient had initially considered radiotherapy in her post-delivery course, but given her most recent PET scan with a Deauville score of less than 4, the patient decided to avoid radiation and opted for close follow-up with repeat imaging. The Deauville 5-point scoring system is an internationally accepted point based scale used to characterize fluorodeoxyglucose (FDG) avidity of malignant tumor mass as seen on FDG positron emission tomography (PET) scan. Scores between 1 and 2 are considered negative, a score of 3 is typically paired with other studies and clinical signs to determine progression of disease, a score of 4 and 5 are considered positive for malignancy progression. Her pericardial effusion had resolved with chemotherapy.

Echocardiographic cardiac strain evaluation performed during follow-up evidenced a drop in her longitudinal strains from 22.8 to -15% just prior to delivery. Ejection fraction remained preserved at >60%. Low-dose carvedilol was considered during treatment however patient was not agreeable. The patient had an uneventful delivery and strain studies post-delivery showed a stable -15% strain. Echocardiogram performed 6 months post-chemotherapy demonstrated an ejection fraction of 72% and normalization of longitudinal strain. In the light of chemotherapy with known cardiotoxic adverse effects, as well as pregnancy strain on cardiac function, the patient did well and underwent an uneventful course.

Discussion 

The majority of data on maternal and fetal cardiotoxic effects of chemotherapy during pregnancy is based on case reports and retrospective data collection (2).

Registry data seems to suggest that the incidence of toxic side effects is not significantly increased during pregnancy and in the current literature there is no mention of an increased frequency of heart failure or left ventricular dysfunction during pregnancy (3-5). A study by Van Calsteren et al. (6), suggested that serum levels of chemotherapy, including anthracyclines, measured in pregnant women, were lower compared with those in nonpregnant women although the differences were not statistically significant. Despite the lower serum levels, cardiotoxicity might have a more significant impact on the maternal cardiovascular system in a context of increased hemodynamic loading. The use of cardiotoxic medications during pregnancy requires further attention, however no standard cardiac follow-up protocols are currently in place (7).

There may be a need for clinical cardiac assessments and an echocardiographic functional evaluation, including cardiac strain monitoring, prior to starting chemotherapy and repeat echocardiographic evaluation prior to every dose. If changes in cardiac function are observed, less cardiotoxic treatments might be considered or cardioprotective agents could be used. In this particular patient population, baseline echocardiography with strain study is crucial. Evidence of abnormal strain study during any part of the treatment should prompt initiation of cardioprotective therapy as per standards of the current heart failure guidelines. In addition, we suggest consideration for close cardiac follow-up monitoring, including a repeat echocardiogram study at 12 months post completion of chemotherapy/radiotherapy treatment. It is still unclear whether prophylactic therapy with cardioprotective agents would be safe and beneficial in these patients. Though we may be able to extrapolate data from trials performed on non-pregnant patients undergoing therapy and apply it to this particular niche of patients. The 2013 ACC/AHA heart failure guidelines state that it may be reasonable to evaluate those who are receiving (or who have received) cardiotoxic chemotherapy agents for left ventricular dysfunction as well as use echocardiographic techniques or biomarkers to identify increased heart failure risk in those receiving chemotherapy (8). In addition, the 2012 European Society of Medical Oncology (ESMO) guidelines stress on importance of serials cardiac function monitoring at baseline, 3, 6 and 9 months during treatment and then at 12 and 18 months after initiation of treatment (9).

Today, there is still no clear consensus with regards to cardioprotective therapy in patients exposed to cardiotoxic agents. As of 2016, the ACC/AHA guidelines did not reflect any change in recommendations in this particular field. Risk-stratification and prophylactic cardioprotective therapy remain an ultimate goal in pregnant patients undergoing chemotherapy, but how that should be done is still being studied. Early cardiology involvement and possible early initiation of prophylactic heart failure therapy should be considered.

References

1. Fadol AP, Lech T, Bickford C, Yusuf SW. Pregnancy in a patient with cancer and heart failure: challenges and complexities. J Adv Pract Oncol. 2012 Mar;3(2):85-93. [PubMed]
2. Gziri MM, Amant F, Debiève F, Van Calsteren K, De Catte L, Mertens L. Effects of chemotherapy during pregnancy on the maternal and fetal heart. Prenat Diagn. 2012 Jul;32(7):614-9. [CrossRef] [PubMed]
3. Cardonick E, Dougherty R, Grana G, Gilmandyar D, Ghaffar S, Usmani A. Breast cancer during pregnancy: maternal and fetal outcomes. Cancer J. 2010;16(1):76-82. [CrossRef] [PubMed]
4. Van Calsteren K, Heyns L, De Smet F, et al. Cancer during pregnancy: an analysis of 215 patients emphasizing the obstetrical and the neonatal outcomes. J Clin Oncol. 2010 Feb 1;28(4):683-9. [CrossRef] [PubMed]
5. Cardonick E, Iacobucci A. Use of chemotherapy during human pregnancy. Lancet Oncol. 2004 May;5(5):283-91. [CrossRef] [PubMed]
6. Van Calsteren K, Verbesselt R, Ottevanger N, et al. Pharmacokinetics of chemotherapeutic agents in pregnancy: a preclinical and clinical study. Acta Obstet Gynecol Scand. 2010 Oct;89(10):1338-45. [CrossRef] [PubMed]
7. Ewer MS, Ewer SM. Cardiotoxicity of anticancer treatments: what the cardiologist needs to know. Nat Rev Cardiol. 2010 Oct;7(10):564-75. [CrossRef] [PubMed]
8. Yancy CW, Jessup M, Bozkurt B, et al. 2013 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013 Oct 15;128(16):1810-52. [CrossRef] [PubMed]
9. Curigliano G, Cardinale D, Suter T, et al. Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO Clinical Practice Guidelines. Ann Oncol. 2012 Oct;23 Suppl 7:vii155-66. [CrossRef] [PubMed]

Cite as: Pak S, Yatsynovich Y, Valencia D, Bushch C, Vannorsdall E. Treatment of lymphoma and cardiac monitoring during pregnancy. Southwest J Pulm Crit Care. 2017;15(4):154-8. doi: https://doi.org/10.13175/swjpcc106-17 PDF 

October 2017 Pulmonary Case of the Month

Eric A. Jensen, MD

Department of Radiology

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 56-year-old woman presented with 3 days of non-productive cough, low-grade fever and severe right-sided pleuritic chest pain.

Past Medical History, Social History and Family History

She was diagnosed with coccidioidomycosis 5 years previously. She reports that she has had pneumonia every 6 to 12 months since her diagnosis with valley fever. She does not smoke. Family history is noncontributory.

Physical Examination

Her vital signs were unremarkable and she was afebrile but did cough frequently during the examination. Her lungs were clear and the rest of the physical examination was unremarkable.

Chest Radiography

She brings in two prior chest x-rays, one from 2011 (Figure 1, Panels A & B) and another from 2012 (Figure 1, Panel C).

Figure 1. Chest radiograph from 2011 (A & B) and from 2012 (C).

Which of the following best describes the chest x-rays? (Click on the correct answer to proceed to the second of five pages)

1. A repeat chest x-ray should be performed
2. A right lower lobe mass is present which appears to have enlarged from 2011 to 2012
3. There is a right lower posterior lung density
4. 1 and 3
5. All of the above

Cite as: Jensen EA. October 2017 pulmonary case of the month. Southwest J Pulm Crit Care. 2017;15(4):125-30. doi: https://doi.org/10.13175/swjpcc115-17 PDF

September 2017 Pulmonary Case of the Month

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 67-year-old woman with history of chronic lymphocytic leukemia (CLL) was referred due to a 6-week history severe cough. Her CLL had recently relapsed and she was begun on ibrutinib (a small molecule drug that binds permanently to Bruton's tyrosine kinase) in addition to acyclovir, sulfamethoxazole/trimethoprim and allopurinol.

Past Medical History, Social History and Family History

Her CLL was initially diagnosed in 2009 and had responded to fludarabine, cyclophosphamide, and rituximab. She had no other chronic medical diseases. She smoked ½ pack per day but quit with the development of her cough. Family history was noncontributory.

Physical Examination

Her vital signs were unremarkable and she was afebrile but did cough frequently during the examination. There were shoddy small lymph nodes noted in both supraclavicular and axillary areas. Lungs were clear and the rest of the physical examination was unremarkable.

Laboratory Evaluation

Her complete blood count revealed her to be mildly anemic with a hemoglobin of 9.0 g/dL, an elevated white count of 33,700 cells/mcL with 88% lymphocytes, and a low platelet count of 60,000 cells/mcL. Her electrolytes were within normal limits and her blood urea nitrogen was 20 mg/dL, creatinine 1.1 mg/dL and uric acid 7.1 mg/dL.

Chest Radiography

A chest x-ray was performed (Figure 1).

Figure 1. Initial chest x-ray.

Which of the following is true? (Click on the correct answer to proceed to the second of five pages)

1. A pulmonary nodule is present in the left upper lobe (LUL)
2. Ibrutinib is well known to cause a chronic cough
3. Pneumonia is unlikely since she is afebrile
4. 1 and 3
5. All of the above

Cite as: Wesselius LJ. September 2017 pulmonary case of the month. Southwest J Pulm Crit Care. 2017;15(3):94-9. doi: https://doi.org/10.13175/swjpcc108-17 PDF