May 2014 Pulmonary Case of the Month: Stress Relief

Robert W. Viggiano, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ

History of Present Illness

A 62 year old man was referred for an abnormal CT scan of the chest. He was found to have an abnormality in the lung as an incidental finding on a CT scan of the abdomen done 6 months earlier for abdominal pain. A CT-guided needle biopsy was performed but revealed only scant tissue and no diagnosis was made.

The patient was asymptomatic without dyspnea, wheezing or cough. He had no fevers, chills, history of pneumonia or sinus disease. He denied any symptoms of gastroesophageal reflux disease (GERD), regurgitation, dysphagia or aspiration.

PMH, FH, SH

The patient had a small melanoma excised from his arm several months earlier. Family history was noncontributory. He smoked a pack per day for 7 years but quit over 30 years earlier. He does not drink.

Medications

• Vitamins
• Mineral oil laxative

Physical Examination

Physical examination was unremarkable.

Radiography

A CT scan of the chest was performed (Figure 1).

Figure 1. Representative images from the thoracic CT scan. Panels A-E: lung windows. Panels F-J: Corresponding soft tissue windows.

The thoracic CT shows which of the following abnormalities? (Click on the correct answer to proceed to the next panel)

1. Left lower lobe mass
2. Mediastinal mass
3. Right middle lobe mass
4. 1 and 3
5. All of the above

Reference as: Viggiano RW. Pulmonary case of the month: stress relief. Southwest J Pulm Crit Care. 2014;8(5): . doi: http://dx.doi.org/10.13175/swjpcc046-14 PDF

Giant Cell Myocarditis: A Case Report and Review of the Literature

Nathan Spence, MD

Karen Niehaus, MD

Leonardo Macias, MD

Bart Cox, MD

University of New Mexico Hospital

Albuquerque, New Mexico, United States

Introduction 

First described by Saltykow in 1905 (1), Giant cell myocarditis (GCM) is a rare but highly lethal disease. Until the 1980s the diagnosis of GCM was determined at autopsy (2). It often affects young patients (mean age of 42.6 + 12.7 years),  and appears to occur in men and women equally. The occurrence of GCM in minority patients has not been previously described (3). The most common presenting symptom is heart failure (75%), though ventricular tachycardia (14%), chest pain with ECG findings of acute myocardial infarction (6%) and complete heart block (5%) may also occur. Treatment often involves an immunosuppressive regimen as a bridge to heart transplantation. The prevalence of GCM is known primarily from autopsy studies (i.e., 0.051% in India, 0.007% in England,  and 0.023% in Japan) (4-6). In the largest GCM observational study yet published, the rate of death or cardiac transplantation was 89 percent, with a median survival of 5.5 months from the onset of symptoms to the time of death or transplantation (3). Few cases with the successful treatment of GCM have been reported (7). Here we describe a case of GCM in a Hispanic female, the first to our knowledge, in which immediate diagnosis and initiation of an immunosuppressive regimen led to a favorable hospital course, whereby she was clinically stabilized and able to be transferred for transplant evaluation.

Case

A 56-year-old Hispanic female with a past medical history significant only for hypertension presented to our emergency department for evaluation of a non-productive cough over the last 3 days, which was associated with a headache, runny nose, myalgias, nausea, vomiting, chest pain, increased dyspnea on exertion, and lower extremity edema. On initial evaluation, heart rate was 86, blood pressure was 131/84, temperature was 37.4 degrees Celsius, oxygen saturation 96% on room air. Physical exam revealed a patient in moderate distress, a pericardial friction rub, clear lungs, and trace lower extremity edema. Laboratory testing revealed a leukocytosis of 12,800/mm³ (normal < 10,600/mm³), troponin I of 3.020 ng/mL (normal < 0.06 ng/mL), N-Terminal-Pro-BNP of 9,775 pg/mL (normal < 125 pg/mL), elevated ESR of 43 mm/hr (normal < 15mm/hr), elevated CRP of 3.6mg/dL (normal < 1 mg/dL), and a mild eosinophilia of 6% (normal < 5%).  Respiratory viral panel was negative. Chest X-Ray revealed a globular cardiac silhouette without definite evidence of congestion. Twelve-lead electrocardiogram revealed normal sinus rhythm with a new left bundle branch block. Cardiac catheterization revealed no significant coronary stenosis, with a left ventricular end diastolic pressure (LVEDP) of 22 mmHg. Upon admission to the floor, diuresis and titration of guideline based medications for dilated cardiomyopathy were begun, but were promptly discontinued due to development of hypotension. Transthoracic echocardiography (TTE) displayed severe hypokinesis of the basal inferoseptum and inferior wall of the left ventricle. Estimated ejection fraction was 35%, with mild to moderate mitral regurgitation. Blood pressure stabilized on day 2 of admission. Cardiac MR (CMR) with gadolinium was ordered, which did not show definite myocardial delayed enhancement (i.e., no evidence of infarction, myocarditis. See Figure 1).

Figure 1 Cardiac Magnetic Resonance Imaging. (A) Two chamber delayed post-gadolinium inversion recovery view. (B) Two chamber delayed post-gadolinium phase sensitive inversion recovery view.

On day 3 of hospitalization, the patient suddenly developed complete heart block, became hypotensive and confused. As a result, a temporary venous pacemaker (TVP) was placed, and endomyocardial biopsy (EMB) was performed. Five specimens were obtained. Pulmonary capillary wedge pressure was measured at 32 mmHg, with a Fick cardiac output 3.01 L/min and cardiac index of 1.77 L/min/m². Due to persistent hypotension in the cath lab, a dopamine drip was begun, a Swan-Ganz catheter was placed, and the patient was transferred to the Medical Intensive Care Unit for further hemodynamic monitoring and treatment. That afternoon, GCM was diagnosed by pathology (see Figure 2).

Figure 2 Pathology. (A) Infiltration of cardiac muscle tissue by an inflammatory infiltrate. (B) Massive myocyte necrosis with giant cells among the inflammatory infiltrate. (C) Rare eosinophils are seen among the inflammatory infiltrate. (D) Giant cell among the inflammatory infiltrate.

An immunosuppressive regimen of corticosteroids, azathioprine,  and cyclosporine was promptly initiated. Thereafter, over the course of 3 days, clinical symptoms  and hemodynamics improved significantly. TVP was removed, inotropic support was weaned off, and ACE inhibitor and diuretics were titrated. Beta-blockers were withheld out of concern for recent complete heart block and use of inotropic support. On hospital day 10, the patient was transferred, in stable condition, to be evaluated for heart transplantation, and/or mechanical circulatory support. At the outside center, she had an ICD placed for primary prevention, was maintained on the three drug immunosuppression regimen, continued to do well clinically, and was listed for transplant.

Discussion

Several autoimmune disorders have been associated with GCM, which include inflammatory bowel disease, thyroiditis, and thymoma (8). Our patient did not have a history of autoimmune disease, and the laboratory tests to detect such during her hospitalization were negative. Evidence suggests that GCM is an autoimmune disorder dependent on CD4-positive T lymphocytes and anti-myosin autoantibodies (8). Early diagnosis leading to appropriate treatment, as in our case, appears to be imperative for a favorable clinical outcome. Treatment with a combination of immunosuppressives has been shown to improve survival, compared with those not receiving immunosuppressive regimens (12.3 months vs. 3.0 months, p=0.001) (3). If patients live long enough to receive heart transplantation, longer term survival is possible. For that reason, it is a Class I (level of evidence B) guideline recommendation to perform EMB in the setting of unexplained, new-onset heart failure of < 2 weeks' duration associated with a normal sized or dilated left ventricle in addition to hemodynamic compromise (9). The sensitivity of EMB for GCM is 80% to 85% in subjects who subsequently die or undergo heart transplantation (2). Therefore, in the appropriate clinical setting, EMB may drastically alter treatment and provide important prognostic information. The pathological hallmark of GCM is the presence of multinucleated giant cells and a lymphocytic inflammatory infiltrate, associated with myocyte necrosis (10-12). CMR may display delayed myocardial enhancement to support the diagnosis of myocarditis, though a non-diagnostic study, as in our case, does not rule it out.   

We encountered, to our knowledge, the first case of GCM in a patient of Hispanic ethnicity, who presented with the classic associated symptoms of heart failure, hemodynamic collapse, and complete heart block, and whose clinical course was favorably improved by early diagnosis and initiation of an immunosuppressive regimen. CMR did not identify myocarditis. However, this case illustrates the importance of including GCM in the differential diagnosis when a patient presents with suggestive clinical features and is not responding to current evidence based treatment for acute decompensated heart failure.

References

1. Saltykow S. Uber Diffuse Myokarditis. Virchows Archiv fur Pathologische Anatomie. 1905;182:1-39. [CrossRef]
2. Shields RC, Tazelaar HD, Berry GJ, Cooper LT. The role of right ventricular endomyocardial biopsy for idiopathic giant cell myocarditis. J Card Fail. 2002;8:74-88. [CrossRef] [PubMed] 
3. Cooper LT, Berry GJ, Shabetai R. Idiopathic giant-cell myocarditis - natural history and treatment. Multicenter Giant Cell Myocarditis Study Group Investigators. N Engl J Med. 1997;336:1860-6.[CrossRef] [PubMed]
4. Vaideeswar P, Cooper L. Giant cell myocarditis: clinical and pathological disease characteristics in an indian population. Cardiovasc Pathol. 2013;22:70-4. [CrossRef] [PubMed]  
5. Whitehead R. Isolated myocarditis. Brit Heart J 1965;27:220-30. [CrossRef] [PubMed]
6. Okada R, Wakafuji S. Myocarditis in autopsy. Heart Vessels 1985; Suppl 1:23-9. [CrossRef]
7. Desjardins V, Pelletier G, Leung TK, Waters D. Successful treatment of severe heart failure caused by idiopathic giant cell myocarditis. Can J Cardiol. 1992;8:788-92. [PubMed] 
8. Cooper L, ElAmm C. Giant Cell Myocarditis: Diagnosis and treatment. Herz. 2012;37:632-6. [CrossRef] [PubMed] 
9. Cooper LT, Baughman KL, Feldman AM, et al. The role of endomyocardial biopsy in the management of cardiovascular disease. A scientific statement from the American heart association, the American college of cardiology, and the European society of cardiology. J Am Coll Cardiol. 2007;50(19):1914-31. [CrossRef] [PubMed] 
10. Davies M, Pomerance A, Teare R. Idiopathic giant cell myocarditis - a distinctive clinico-pathological entity. Br Heart J. 1975;37:192-5. [CrossRef] [PubMed] 
11. Davidoff R, Palacios I, Southern J, Fallon JT, Newell J, Dec GW. Giant cell versus lymphocytic myocarditis. A comparison of their clinical features and long-term outcomes. Circulation. 1991;83:953-61. [CrossRef] [PubMed] 
12. Ren H, Poston RS Jr, Hruban RH, Baumgartner WA, Baughman KL, Hutchins GM. Long survival with giant cell myocarditis. Mod Pathol. 1993;6:402-7. [PubMed] 

Reference as: Spence N, Niehaus K, Macias L, Cox B. Giant cell myocarditis: a case report and review of the literature. Southwest J Pulm Crit Care. 2014;8(4):247-51. doi: http://dx.doi.org/10.13175/swjpcc052-14 PDF

April 2014 Pulmonary Case of the Month: DIP-What?

Lewis Wesselius MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ

History of Present Illness

A 53 year old woman from Indiana was seen who had a history of nonproductive cough for several years.  She had a prior diagnosis of asthma but continued to have cough despite asthma treatment.  She was also treated for gastroesophageal reflux and had a Nissen fundoplication.  This resolved in some improvement in the cough. In May 2013 she noted increasing dyspnea on exertion.

An echocardiogram was performed which was notable for a 16% left ventricular ejection fraction. A thoracic CT demonstrated some nodules and a question was raised of sarcoidosis. She was admitted to a hospital in Indiana and had a biventricular pacemaker placed. Bronchoscopy with transbronchial biopsy was performed with no diagnostic findings. No granulomas were seen on the biopsy. Bronchoalveolar lavage showed a CD4/CD8 ration of 0.84. Optic nerve swelling was noted at that time. Due to the cardiac, pulmonary, and optic nerve findings a clinical diagnosis of sarcoidosis with a dilated cardiomyopathy was made and she was treated with prednisone initially, then a combination of prednisone and methotrexate.

PMH, FH, SH

Her past medical history was as above and family history was noncontributory. She does not smoke or drink.

Medications

• Methotrexate 15 mg weekly
• Prednisone 5 mg daily
• Furosemide 40 mg daily
• Potassium chloride 20 meq daily

Physical Examination

Afebrile. SpO2 96% on room air. The physical exam was unremarkable.

Which of the following should be performed at this time?

1. Pulmonary function testing
2. Repeat echocardiogram
3. Repeat thoracic CT scan
4. 1 and 3
5. All of the above

Reference as: Wesselius LJ. April 2014 pulmonary case of the month: DIP-what? Southwest J Pulm Crit Care. 2014;8(4):195-203. doi: http://dx.doi.org/10.13175/swjpcc024-14 PDF

Wireless Capsule Endo Bronchoscopy

 David M. Baratz, MD

Sandra Till, DO

Banner Good Samaritan Medical Center

Phoenix, AZ

Case Presentation

History of Present Illness

A 67 year-old man presents 10 days after swallowing a capsule endoscopy camera that was never retrieved.  The wireless capsule was swallowed asymptomatically for evaluation of heme positive stools after negative upper and lower endoscopies. Patient noted that the evening after swallowing the camera he developed mild shortness of breath and cough. The cough and shortness of breath were persistent and worsened while lying down and when moving positions. He denied prior issues with swallowing or aspiration.

Review of Systems

Negative other than what is noted above.

PMH, SH, and FH

Past medical history: coronary artery disease, peripheral vascular disease, hyperlipidemia

Surgical history: femoral-popliteal bypass, previous shoulder and back surgery

Social history: 1 pack/day of cigarettes for 50 years, prior alcohol usage but not current, no illicit drugs

Family history: no pulmonary diseases

Physical Exam

Vital signs: temperature 36.7º C, heart rate 86 beats per minute, respiratory rate 15 breaths/min, blood pressure 156/69, and oxygen saturation 97% while breathing  room air

Lungs: bilateral wheezing with left greater than right.

Otherwise examination was normal.

Radiography

The admission chest x-ray is shown in figure 1.

Figure 1. Chest x-ray with capsule in left main bronchus (arrow).

A thoracic CT scan is shown in Figure 2.

Figure 2. Thoracic non-contrast CT scan with capsule in left main bronchus (arrow).

Bronchoscopy was performed under general anesthesia using a laryngeal mask airway (LMA). Bronchoscopic examination revealed a white capsule lodged in left main bronchus (Figure 3).

Figure 3. Bronchoscopy with capsule in left main bronchus.

A mesh basket was used to retrieve of the capsule from the left main bronchus, but in the carina the capsule slipped out of the basket. Attempts to use snare and retrieval forceps failed due to the slippery plastic housing covering the capsule.  The mesh basket was used again with capture of the capsule. Once the capsule was retrieved, the LMA was removed to avoid en bloc damage to the vocal cord while removing the capsule. The LMA was then reinserted for continued ventilation after the capsule had been obtained.

Figure 4. Intact capsule after removal.

Literature Review

Capsule endoscopy has been available since 2001 and is used for the evaluation of obscure gastrointestinal bleeding and iron deficiency anemia. The retention rate is 1-2%, with capsules typically found in diverticula, hernias, or other bowel abnormalities (1-3). It is reported that approximately 2% of patients will have difficulty or inability to swallow the capsule.  Review of 13 available cases of aspiration of wireless endoscopy capsules revealed that about 50% of the time capsules are spontaneously expulsed by coughing, and the other half requiring bronchoscopic intervention for removal (Table 1).

Table 1. Summary of cases with aspirated wireless endoscopy capsules.

Risks for aspiration include underlying neurologic disease, elderly patients, and patient with previous difficulties with swallowing. Signs of capsule aspiration vary from asymptomatic to shortness of breath, cough, and tachypnea (1-12).

The capsule is a wirelesses, 11 mm X 26 mm capsule with a miniature video camera, light emitting diodes, batteries, transmitter, and an antenna. It is slippery, nonbiodegradable, has plastic housing, and weighs less than 4 grams (13).

This case represents a rare, but important complication of wireless capsule endoscopy requiring evaluation and possible intervention. Although this complication is rare, it is likely we will see increasing frequency as capsule utilization increases.

References

1. Guy T, Jouneau S, D'Halluin PN, Lena H. Asymptomatic bronchial aspiration of a video capsule. Interact Cardiovasc Thorac Surg. 2009;8(5):568-70. [CrossRef] [PubMed] 
2. Depriest K, Wahla AS, Blair R, Fein B, Chin R Jr. Capsule endoscopy removal through flexible bronchoscopy. Respiration. 2010;79(5):421-4. [CrossRef] [PubMed] 
3. Koulaouzidis A, Pendlebury J, Douglas S, Plevris JN. Aspiration of video capsule: rare but potentially life-threatening complication to include in your consent form. Am J Gastroenterol. 2009;104(6):1602-3. [CrossRef] [PubMed] 
4. Choi HS, Kim JO, Kim HG, Lee TH, Kim WJ, Cho WY, Cho JY, Lee JS. A case of asymptomatic aspiration of a capsule endoscope with a successful resolution. Gut Liver. 2010;4(1):114-6. [CrossRef] [PubMed]
5. Buchkremer F, Herrmann T, Stremmel W. Mild respiratory distress after wireless capsule endoscopy. Gut. 2004;53(3):472. [CrossRef] [PubMed]
6. Ding NS, Hair C, De Cruz P, Watson J. Education and Imaging. Gastrointestinal: symptomatic bronchial aspiration of capsule endoscope - a significant complication. J Gastroenterol Hepatol. 2013;28(5):761. [CrossRef] [PubMed]
7. Nathan SR, Biernat L. Aspiration--an important complication of small-bowel video capsule endoscopy. Endoscopy. 2007;39 Suppl 1:E343. [CrossRef] [PubMed] 
8. Pezzoli A, Fusetti N, Carella A, Gullini S. Asymptomatic bronchial aspiration and prolonged retention of a capsule endoscope: a case report. J Med Case Rep. 2011;5:341. [CrossRef] [PubMed] 
9. Schneider AR, Hoepffner N, Rösch W, Caspary WF. Aspiration of an M2A capsule. Endoscopy. 2003;35(8):713. [CrossRef] [PubMed] 
10. Bredenoord AJ, Stolk MF, Al-toma A.Tabib S, Fuller C, Daniels J, Lo SK. Unintentional video capsule bronchoscopy. Eur J Gastroenterol Hepatol. 2009;21(5):593. [CrossRef] [PubMed] 
11. Tabib S, Fuller C, Daniels J, Lo SK.Sepehr A, Albers GC, Armstrong WB. Asymptomatic aspiration of a capsule endoscope. Gastrointest Endosc. 2004;60(5):845-8. [CrossRef] [PubMed]
12. Sepehr A, Albers GC, Armstrong WB. Aspiration of a capsule endoscope and description of a unique retrieval technique. Otolaryngol Head Neck Surg. 2007;137(6):965-6. [CrossRef] [PubMed]
13. Kelley SR, Lohr JM. Retained wireless video enteroscopy capsule: a case report and review of the literature. J Surg Educ. 2009;66(5):296-300. [CrossRef] [PubMed]

Reference as: Baratz DM, Till S. Wireless capsule endo bronchoscopy. Southwest J Pulm Crit Care. 2014;8(3):183-7. doi: http://dx.doi.org/10.13175/swjpcc014-14 PDF

Elevated Tumor Markers In Coccidioidomycosis of the Female Genital Tract

Ying Wu, MD¹

Stacy Arnold²

Tim Kuberski, MD³

¹Department of Internal Medicine and the ³Section of Infectious Disease

Maricopa Medical Center

Phoenix, Arizona

²University of Arizona College of Medicine Phoenix

Phoenix, Arizona

Abstract

The female genital tract is rarely involved by coccidioidomycosis. We describe a woman with disseminated coccidioidomycosis involving the female pelvic organs associated with elevated tumor markers CA 125 and CA 19-9. She had no fevers and the initial clinical suspicion was a malignancy because of the elevated tumor markers. At exploratory laparotomy a total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed because of the suspicion of a malignancy. Subsequent pathology demonstrated coccidioidomycosis involving the female genital tract and no malignancy. The abnormal CA 125 and CA 19-9 returned to normal after surgical resection and treatment of the coccidioidomycosis.

Introduction

Dissemination of coccidioidomycosis to the female genital tract is an unusual complication of that fungal infection (1). This report describes a woman with disseminated coccidioidomycosis which mimicked a malignancy of the female genital tract. The initial clinical suspicion was a malignancy because of the elevation of carbohydrate antigen tumor markers CA125 and CA19-9.

Case Report

A 48-year-old Hispanic woman with a history of adult onset diabetes and menorrhagia presented with left lower quadrant pain.  She denied fever, chills or sweats.  She gave no history of “Valley Fever” or pneumonia.  Physical examination was significant for left lower quadrant abdominal tenderness without rebound or guarding.  CT of the abdomen and pelvis showed free fluid within the pelvis, masses within the uterus, left hydronephrosis and bilateral cystic masses of the adnexa. She was anemic and thrombocytopenic with a hemoglobin of 7.8 g/dL and platelet count of 51,000/mm³.  She received blood and platelet transfusions and was given oral prednisone 80 mg once daily for five days which was associated with improvement of her platelet count to normal. Certain tumor markers were found to be elevated a CA 125 of 475.7 (normal range: 0-35 U/mL) and CA 19-9 of 133 (normal range: 0–37 U/mL). A carcinoembryonic antigen (CEA) was not elevated 1.9 (normal range 0-2.5 ng/ml). Her diabetes was controlled. The left hydronephrosis was treated with a ureteral stent and nephrostomy.  An endometrial biopsy was consistent with benign endocervical and endometrial tissue.  Percutaneous drainage of the left ovarian cyst fluid showed no malignant cells and no abscess.  A plain chest x-ray was interpreted as normal, however a CT scan of the chest showed a left lower lobe lesion which was biopsied and found to be consistent with an old Coccidioides granuloma.  Because of the concern for a pelvic malignancy, an exploratory laparotomy was done and a total hysterectomy with bilateral salpingo-oophorectomy was performed.  The pathology of the surgical specimen showed Coccidioides with necrotizing granulomas and spherules in the round ligament, uterus, endometrium, bilateral ovaries and fallopian tubes (Figure 1).

Figure 1.  Hematoxylin and eosin stain of round ligament showing necrotizing granulomas associated with Coccidioides spherules (arrows). Empty Coccidioides  spherule in inset.

Following the operation, she was started on oral fluconazole 400mg daily and followed as an outpatient. Her complement fixation titer for Coccidioides was positive at 1:64 on discharge, increased to 1:256 one month later and then declined to 1:8 five months later. At five months follow-up she was asymptomatic and back to her premorbid state. She was to remain on fluconazole indefinitely.  Postoperatively the CA 125 and CA 19-9 returned to normal at 12.3 and 12.0 respectively after fifty days (Table 1). 

Table 1. Tumor Marker Values Before and Fifty Days After Surgical Resection.

                          

Discussion 

Dissemination of Coccidioides to the female pelvic organs is unusual. In a series of 142 necropsies of patients who died of coccidioidomycosis, none of the thirty-three females had involvement of the genital tract (2).  Presumptively the fungus spreads endogenously from the lung as in our patient. It is notable that the lung lesion in this patient was initially thought to be a malignancy. However, when “old Coccidioides granuloma” was reported, it was not associated with her genital tract problem by the treating physicians. We were able to find seventeen previously reported cases of coccidioidomycosis involving the female genital tract since the first report in 1929 (3-7). In those cases of Coccidioides involving the genital tract, there was no combination of investigations or clinical features that were sensitive enough to diagnose the female genital tract infection preoperatively. In fourteen of the eighteen patients (including our patient) with Coccidioides serologic test results, thirteen had a positive titer of 1:16 or greater (3-6).

In all eighteen cases the diagnosis of Coccidioides involving the genital tract was made only post-operatively after the microscopic examination of surgical specimens. Treatment of female genital tract coccidioidomycosis generally requires surgical resection of the involved tissues and antifungal agents (3). Cure of pelvic coccidioidomycosis by surgical resection alone, without antifungal therapy, has been reported in at least 5 cases (3,7). However, deaths attributable to disseminated coccidioidomycosis with involvement of the genital tract despite treatment and surgery have been reported (8). Quantitative serologic testing can be useful in making the diagnosis and following the response to treatment. The complement fixation titers to Coccidioides would be expected to decrease with treatment and clinical improvement. Our patient’s complement fixation titer went from a high of 1:256 to 1:8 after surgical resection and five months of treatment. In general, patients with disseminated coccidioidomycosis will respond to fluconazole, but the duration of therapy can be protracted for years.

Early in the course of our patient’s workup, she was found to have elevated CA 125 and CA 19-9 levels, raising the suspicion of a malignancy. In general, tumor markers should not be used as a screening test for malignancy and are most useful for following the response to treatment. In this patient the response was to antifungal therapy rather than chemotherapy. We believe the tumor markers were elevated due to the inflammatory response to the Coccidioides infection (4,9). CA 125 is most commonly monitored in the management of ovarian carcinoma.  However, it is only 75-80% sensitive in patients with ovarian cancer and can also be elevated in a variety of benign conditions such as infection (10).  In addition to the ovarian cancer cells, benign endometrial and peritoneal mesothelial cells can also secrete CA 125 (11). It appears that any process causing serosal inflammation may elevate CA 125. Thus non-tumorous conditions such as pelvic tuberculosis can result in sufficient inflammation to cause an increased CA 125 level (12). CA 19-9 is a serum marker associated with pancreatic cancer, but it also can be elevated in non-cancerous conditions such as pancreatitis, endometriosis and in diabetics with poor glycemic control (10,13).

Both CA 125 and CA 19-9 can be elevated in noncancerous conditions such as infection and presumed to be the reason for the elevation in our patient. Her surgical histopathology showed concomitant endometriosis of the round ligament, uterine serosa and both ovaries (Figure 2).

Figure 2. Hematoxylin and eosin stain of ovary showing changes consistent with endometriosis (arrow).

This was in addition to the necrotizing granulomas containing Coccidioides spherules (Figure 1). Increased levels of CA 125 have been reported previously in three patients with Coccidioides involving pelvic organs (4,5,7), but there have been no reports of elevated serum CA 19-9 levels.  Endometriosis alone can cause both CA 125 and CA 19-9 to be increased (14,15), however the mechanism by which these markers become elevated is not completely understood. It has been postulated that chronic inflammation causes an epithelial reaction that results in the leakage of the tumor markers into the circulation (14,15).  Endometriosis due to a variety of infectious etiologies can cause serum CA 125 levels to be elevated and they can precipitously decrease following surgical intervention, as in our patient (4,5). CA 19-9 levels have also been found to return to normal following surgical intervention for endometriosis (16). We presume that the elevated tumor markers in our patient were the result of similar inflammatory mechanisms observed for both CA 125 and CA 19-9. We suspect the reason that CA 19-9 levels have not been reported previously is that this test would be ordered less frequently in patients suspected of having a pelvic malignancy. Our patient had a normal CEA level consistent with a lack of involvement of the gastrointestinal tract by coccidioidomycosis.

Another potential source of Coccidioides infecting the female genital tract is sexual transmission. We could find no references to document sexual transmission of Coccidioides. However, transmission from a man with prostate involvement to a woman who developed an infection of her genital tract could occur, but our patient’s husband had no prostate disease, no history of Valley Fever and his Coccidioides serology was negative. Coccidioides has been documented to mimic a variety of malignancies such as breast cancer, bronchogenic carcinoma, osteosarcoma and lymphoma (6). It is notable that the first reported case of coccidioidomycosis in 1892 was initially misdiagnosed as mycosis fungoides (6). Coccidioidomycosis is known to have protean manifestations and in this patient it mimicked a female genital tract malignancy. This case is unique because a Coccidioides infection was documented and associated with the elevation of tumor markers CA 19-9 and CA 125, which returned to normal following treatment and surgical resection of the involved tissues. Involvement of the female genital tract by coccidioidomycosis may be uncommon, but in endemic areas it should be a consideration in the differential diagnosis in women with a suspected pelvic malignancy and elevated levels of CA 125 and CA 19-9.

References

1. Saw EC, Smale LE, Einstein H, Huntington RW,Jr. Female genital coccidioidomycosis. Obstet Gynecol. 1975;45:199-202. [PubMed] 
2. Huntington RW Jr., Waldmann WJ, Sargent JA, O'Connell H, Wybel R, Croll D. pathological and clinical observations in 142 cases of fatal coccidioidomycosis on necropsy. In Ajello L, ed. Proceedings of the Second Coccidioidomycosis Symposium. Tuscon, The University of Arizona Press.1967:143-167.
3. Chowfin A, Tight R. Female genital coccidioidomycosis (FGC), Addison's disease and sigmoid loop abscess due to Coccidioides immites; case report and review of literature on FGC. Mycopathologia. 1999;145:121-126. [CrossRef] [PubMed]
4. Ellis MW, Dooley DP, Sundborg MJ, Joiner LL, Kost ER. Coccidioidomycosis mimicking ovarian cancer. Obstet Gynecol. 2004;104:1177-1179. [CrossRef] [PubMed] 
5. Micha JP, Goldstein BH, Robinson PA, Rettenmaier MA, Brown JV. Abdominal/pelvic Coccidioidomycosis. Gynecol Oncol. 2005;96:256-258. [CrossRef] [PubMed]
6. Crum-Cianflone NF, Truett AA, Teneza-Mora N, et al. Unusual presentations of coccidioidomycosis: a case series and review of the literature. Medicine (Baltimore). 2006;85:263-277. [CrossRef] [PubMed] 
7. Smith G, Hoover S, Sobonya R, Klotz SA. Abdominal and pelvic coccidioidomycosis. Am J Med Sci. 2011;341:308-311. [CrossRef] [PubMed]
8. Bylund DJ, Nanfro JJ, Marsh WL,Jr. Coccidioidomycosis of the female genital tract. Arch Pathol Lab Med. 1986;110:232-235. [PubMed] 
9. Bast RC,Jr, Xu FJ, Yu YH, Barnhill S, Zhang Z, Mills GB. CA 125: the past and the future. Int J Biol Markers. 1998;13:179-187. [PubMed] 
10. Cancer antigen 125. In: Ferri FF, ed. Ferri's Clinical Advisor 2013 : 5 Books in 1. 1st ed. St. Louis, Mo: Elsevier Mosby; 2013:1452-1453.
11. Sevinc A, Camci C, Turk HM, Buyukberber S. How to interpret serum CA 125 levels in patients with serosal involvement? A clinical dilemma. Oncology. 2003;65:1-6. [CrossRef] [PubMed] 
12. Sheth SS. Elevated CA 125 in advanced abdominal or pelvic tuberculosis. Int J Gynaecol Obstet. 1996;52:167-171. [CrossRef] [PubMed]
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Reference as: Wu Y, Arnold S, Kuberski T. Elevated tumor markers in coccidiomyocosis of the female genital tract. Southwest J Pulm Crit Care. 2014;8(3):170-5. doi: http://dx.doi.org/10.13175/swjpcc179-13 PDF