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Coccidioidomycosis of the prostate gland: two cases and a review of the literature.


Abstract: Coccidioidomycosis prostatitis is an uncommon presentation of disseminated coccidioidomycosis, a fungal disease endemic in the southwestern United States. Coccidioidomycosis prostatitis should be considered in the differential diagnosis of a patient from an endemic region with evidence of persistent sterile pyuria, prostatitis, or granulomatous disease of the prostate. Diagnosis is established by biopsy, and treatment includes either an azole or amphotericin B. We present the twelfth and thirteenth reported cases and provide a review of the literature.

Key Words: acute splenic sequestration crisis, adults, sickle cell anemia

**********

Coccidioidomycosis, or valley fever, is acquired by inhalation of arthroconidia in desert soil in the southwestern United States. Clinical manifestations are typically a flu-like illness or self-limited pneumonia; 1 to 5% of patients with the condition develop disseminated disease, which most commonly involves the skin, bones/joints, and central nervous system. Coccidioides immitis prostatitis is a rare form of disseminated coccidioidomycosis. To the best of our knowledge, only 11 antemortem cases of coccidioidomycosis prostatitis have been reported in the medical literature. We present the 12th and 13th cases and provide a review of the literature.

Case Reports

Patient 1

A 65-year-old black man presented to the urology clinic in August 1999 for evaluation of a prostate nodule and a rising prostate-specific antigen level that hadincreased from 2.0 ng/mL to 4.1 ng/mL. A prostate biopsyrevealed focal granulomatous inflammation, with fungal elements consistent with Coccidioides immitis (Fig. 1). The patient was lost to follow-up, without receiving any antifungal therapy. In November 2002, the patient presented to his primary care physician who, on review of the biopsy result, referred him to our infectious disease clinic for further evaluation.

The patient had no complaints of dysuria, hematuria, frequency, or hesitancy. He reported no history of prior coccidioidomycosis or pulmonary complaints. The patient had spent his childhood in eastern Texas and moved to the Central Valley of California, where he lived for many years before moving to San Diego, CA, in 1978. He had a history of hypertension, hyperlipidemia, osteoarthritis, and a positive purified protein derivative test in 1968, for which he had received 1 year of isoniazid therapy. In August 2001, the patient had a 1-cm, flat, itchy "fungal infection" of the right buttock that resolved after 4 weeks of oral fluconazole at a dose of 200 mg weekly.

Physical examination was unremarkable except for the prostate gland, which had a nodular surface but was nontender and not enlarged. The skin examination was normal. Complete blood count and chemistries were normal. Serum C. immitis enzyme immunoassay was positive for immunoglobulin G and immunoglobulin M, and his complement fixation (CF) titer was 1:64. Urinalysis revealed sterile pyuria, and urine fungal cultures grew C. immitis. Chest radiography revealed linear opacities extending from the left hilum, consistent with scarring, and a bone scan was normal. The patient was treated with oral fluconazole 800 mg daily and is currently well.

Patient 2

A 53-year-old white man with adult-onset diabetes was evaluated in 1989 for epididymal and prostate masses. He was a long-term resident of southern California and had been an archeological student in the 1970s. Several of his classmates had developed coccidioidomycosis, but he had no clinical or skin test evidence of infection at that time. During the 1980s, he was repeatedly evaluated for neutrophilia of unknown cause. During an evaluation by a urologist in 1989, a prostate biopsy to evaluate for suspected prostate malignancy revealed granulomatous inflammation and C. immitis spherules. The patient denied any systemic complaints. The CF titer on diagnosis was 1:32, and a chest radiograph and bone scan were unremarkable. He was treated with daily oral fluconazole, with clinical resolution and decreasing CF titers. He is currently on fluconazole 400 mg/d, with a titer of less than 1:2. He remains asymptomatic with respect to his coccidioidomycosis after 10 years of follow-up.

Discussion

Coccidioidomycosis prostatitis is an uncommon presentation of disseminated coccidioidomycosis, a fungal disease endemic in the southwestern United States and parts of South and Central America. Coccidioidomycosis may affect any organ; however, the most common sites of dissemination include the skin, bones, joints, and meninges. Genitourinary coccidioidomycosis, a form of disseminated disease, may involve the prostate, kidneys, bladder, and reproductive organs, and may go undiagnosed among patients with more prominent signs of disseminated disease in other organs. The kidney is the sixth most common site of dissemination, and Forbus and Bestebreurtje (1) found renal involvement in up to 60% of patients with disseminated disease at autopsy--6% had prostatic disease. Prostate involvement is rarely recognized antemortem.

We performed a MEDLINE search of the English literature from 1966 to 2002 and examined the Index Medicus from 1940 to 1966 using the search terms "coccidioidomycosis," "prostate," "prostatitis," and "genitourinary." McDougall and Kleinman (2) described the first antemortem case of coccidioidomycosis prostatitis in 1943, and an additional 12 cases have been added to the medical literature, including the two cases we present here (Table 1). (2-11) The median age at the time of diagnosis of coccidioidomycosis prostatitis was 62 years (range, 44-72 years). Sixty-two percent of the patients were white, 15% were black, 15% were Hispanic, and 8% were Filipino.

[FIGURE 1 OMITTED]

Coccidioidomycosis prostatitis may be asymptomatic or may present with symptoms attributed to the urinary system. Of the 13 antemortem reported cases, 5 (38%) reported no urologic symptoms, 4 (31%) had symptoms of bladder outlet obstruction, 1 (8%) reported hematuria, and 1 (8%) reported an epididymal mass; in 2 (15%), symptoms were not reported. Prostate examination may be normal or may reveal tenderness, bogginess, firmness, or the presence of one or more nodules. Of the 11 cases that included a description of the prostate examination, prostatic enlargement was reported in 6 (55%), prostate nodules in 4 (36%), and a normal prostate examination in 1 (9%). The prostate-specific antigen level is frequently elevated as a result of the local inflammation caused by the fungal infection.

Urinalysis is often abnormal; of the 10 patients with a documented urinalysis, 6 (60%) had pyuria, 1 (10%) had hematuria, 1 (10%) had bacteruria, and 2 (20%) had normal specimens. Characteristic C. immitis spherules may be visualized in concentrated urine specimens, expressed prostatic secretions or, more commonly, in biopsy specimens. The organism may also be grown in culture from any of the above specimens. C. immitis grew in urine fungal cultures in 5 of 13 cases (38%). Definitive diagnosis, however, is made by pathologic tissue examination in which the characteristic endospore-containing spherules are seen. Periodic acid-Schiff (PAS) and silver-methenamine stains are the most reliable, although the organism may at times be seen with a routine hematoxylin and eosin stain. CF titers were reported in 10 of the patients, and 6 of 10 (60%) had a coccidioides CF titer greater than or equal to 1:32. Radiographic studies are not helpful in the diagnosis of coccidioidomycosis prostatitis.

There are no specific guidelines for the treatment of coccidioidomycosis prostatitis; however, daily oral fluconazole 800 mg followed by long-term suppressive therapy is advocated. For disseminated disease involving other extrapulmonary sites, initial intravenous amphotericin B is usually indicated. Although surgical procedures are occasionally indicated for symptomatic or concomitant disease, such procedures are not typically curative, and adjunctive systemic antifungal therapy is indicated. Regular monitoring of serum coccidioides CF titers is warranted to follow the response to therapy.

Conclusion

Coccidioidomycosis prostatitis, although uncommon, should be considered in the differential diagnosis of any patient from an endemic region with evidence of persistent sterile pyuria, prostatitis, or granulomatous disease of the prostate. If identified, coccidioidomycosis prostatitis should be treated aggressively, as it always represents disseminated disease.
Table 1. Coccidioidomycosis of the prostate, 1940-2002 (a)

                                                         Time from
                                                         initial
                                                         diagnosis
        Series        Age                                to prostate
Case  (ref. no.)     (yr)  Race      Symptoms/signs      involvement

 1    McDougall       52   White     Hematuria, history  Unclear
        and                            of cough,
        Kleimar,                       sweats, weight
        1943 (2)                       loss
 2    Gritti et al,   48   White     Weight loss, knee   Unclear
        1963 (3)                       pain
 3    Bellin and      72   White     Outlet obstruction  None
        Bhavan,
        1973 (4)
 4    Gottesman,      72   White     Urgency, outlet     None
        1974 (5)                       obstruction
 5    Petersen et     44   Black     NR                  Unclear
        al, 1976
        (6)
 6    Petersen et     45   White     NR                  Unclear
        al, 1976
        (6)
 7    Sung et al,     62   Mexican   Hemoptysis          6 yr earlier
        1979 (7)
 8    Price et al,    72   Filipino  Weight loss,        Same time
        1982 (8)                       urinary
                                       obstructive
                                       symptoms
 9    Chen and        67   White     Nocturia, urinary   20 yr
        Schiff,                        obstructive
        1985 (9)                       symptoms
10    Niku et al,     54   White     Weight loss and     Earlier date
        1998 (10)                      cough
11    Lawrence et     62   Cuban     None                4 yr
        al, 1999
        (11)
12    Truett and      65   Black     None                Same time
        Crum,
        2004
        (present
        study)
13    Truett and      53    White    Epididymal mass     Same time
        Crum,
        2004
        (present
        study)

                          Sites of
         Series        nongenitourinary
Case   (ref. No.)        involvement      Examination      Urinalysis

 1     McDougall       Meninges, knee,    Enlarged,        Hematuria
         and             possibly lung      asymmetric
         Kleimar,                           prostate
         1943 (2)
 2     Gritti et al,   Lung, knee         Prostate         Normal
         1963 (3)                           nodule
 3     Berlin and      None               Enlarged         Pyuria
         Bhavan,                            prostate
         (1973) (4)                         with hard
                                            areas
 4     Gottesman,      None               Normal           Bacteriuria
         (1974) (5)
 5     Petersen et     Lung, meninges,    NR               Pyuria and
         al, 1976        spleen                              proteinuria
         (6)
 6     Petersen et     Lung, meninges,    NR               Pyuria and
         al, 1976        spleen                              proteinuria
         (6)
 7     Sung et al,     Possibly lung      Tender, nodular  Pyuria
         (1979) (7)                         prostate
 8     Price et al,    None               Diffusely        NR
         (1982) (8)                         enlarged
                                            prostate
 9     Chen and        Pulmonary          Diffusely        Pyuria
         Schiff,                            enlarged
         (1985) (9)                         prostate
10     Niku et al,     Possibly lung      Enlarged         NR
         (1998) (10)                        prostate
11     Lawrence et     None               Firm prostate    NR
         al, 1999                           with nodule
         (11)
12     Truett and      Possibly lung      Prostate         Pyuria
         Crum,                              nodule
         2004
         (present
         study)
13     Truett and      None               Enlarged,        Normal
         Crum,                              hard
         2004                               prostate
         (present
         study)

        Series         PSA        CF            Cultures/
Case  (ref. No.)     (ng/ml)    titer        pathologic findings

 1    McDougall         NR        NR         Spherules on
        and                                    prostate abscess
        Kleimar,                               drainage; positive
        1943 (2)                               urine cultures
 2    Gritti et al,     NR         1:        Spherules on
        1963 (3)                  16           prostate biopsy
 3    Bellin and        NR         1:        Spherules on TURP
        Bhavan,                   64           specimen (b)
        1973 (4)
 4    Gottesman,        NR         1:1       Spherules on
        1974 (5)                               prostatectomy
                                               specimen
 5    Petersenet        NR         1:        Spherules on
        al, 1976                 128           prostate biopsy;
        (6)                                    positive urine
                                               cultures
 6    Petersen et       NR         1:        Spherules on
        al, 1976                  64           prostate abscess
        (6)                                    drainage; positive
                                               urine cultures
 7    Sung et al,       NR         1:        Spherules on
        1979 (7)                 128           prostate biopsy;
                                               positive urine
                                               cultures
 8    Price et al,      NR         1:4       Spherules on TURP
        1982 (8)                               specimen; no
                                               cultures
 9    Chen and          NR         1:        Spherules on TURP
        Schiff,                   16           specimen; no
        1985 (9)                               cultures
10    Niku et al,       9.2       NR         Spherules on
        1998 (10)                              prostatectomy
                                               specimen (b)
11    Lawrence et      14.7       NR         Spherules on
        al, 1999                               prostatectomy
        (11)                                   specimen (b)
12    Truett and        4.1        1:        Spherules on
        Crum,                     64           prostate biopsy
        2004                                   specimen:
        (present                               positive urine
        study)                                 cultures
13    Truett and        NP         1:        Spherules on
        Crum,                     32           prostate biopsy
        2004                                   specimen
        (present
        study)

       Series        Chest
Case  (ref. no.)     radiograph       Therapy          Outcome

 1    McDougall      Atypical         Neoprontosil     Died as a
        and            tuberculosis                      result of
        Kleimar,                                         meningitis
        1943 (2)
 2    Gritti et al,  Coin lesion      Amphotericin B   No follow-up
        1963 (3)
 3    Bellin and     Pulmonary        Transurethral    No follow-up
        Bhavan,        fibrosis         resection
        1973 (4)       with
                       bilateral
                       pleural
                       effusions
 4    Gottesman,     NR               Amphotericin B   Well at 6 mo
        1974 (5)
 5    Petersen et    NR               Amphotericin B   Died
        al, 1976
        (6)
 6    Petersen et    NR               Amphotericin B   Died
        al, 1976
        (6)
 7    Sung et al,    Normal           Amphotericin B   Well at 8 mo
        1979 (7)                        2.5 g and
                                        transurethral
                                        resection
 8    Price et al,   Normal           Amphotericin     Well
        1982 (8)                        800 mg and
                                        transurethral
                                        resection
 9    Chen and       Normal;          Ketoconazole     Well at 18 mo
        Schiff,        history
        1985 (9)       of pneumonia
10    Niku et al,    NR               Fluconazole      Well
        1998 (10)                       800 PO
                                        every day
11    Lawrence et    NR               Antifungal oral  Well
        al, 1999                        medication
        (11)
12    Truett and     Hilar scarring   Fluconazole      Well at 3
        Crum,                           800 mg/d         mo
        2004
        (present
        study)
13    Truett and     Normal           Fluconazole      Well at 10
        Crum,                           400 mg/d         yr
        2004
        (present
        study)

(a) NR, not reported; NP, not performed; TURP, transurethral
prostatectomy.
(b) Also diagnosed with prostate adenocarcinoma.


Acknowledgment

The authors would like to express their gratitude to Dr. Mark Wallace for his critical review of the manuscript.

Accepted October 22, 2003.

Copyright [c] 2004 by The Southern Medical Association

0038-4348/04/9704-0419

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 1946:99:653-671.

2. McDougall TG, Kleiman AH. Prostatitis due to Coccidioides immitis. J Urol 1943:49:472-477.

3. Gritti EJ, Cook FE Jr, Spencer HB. Coccidioidomycosis granuloma of the prostate: A rare manifestation of the disseminated disease. J Urol 1963;89:249-252.

4. Bellin HJ, Bhagavan BS. Coccidioidomycosis of the prostate gland: Report of a case and review of the literature. Arch Pathol 1973;96:114-117.

5. Gottesman JE. Coccidioidomycosis of prostate and epididymis: With urethrocutaneous fistula. Urology 1974;4:311-314.

6. Petersen EA, Friedman BA, Crowder ED, et al. Coccidoidouria: Clinical significance. Ann Intern Med 1976;85:34-38.

7. Sung JP, Sun SS, Crutchlow PF. Coccidioidomycosis of the prostate gland and its therapy. J Urol 1979;121:127-128.

8. Price MJ, Lewis EL, Carmalt JE. Coccidioidomycosis of prostate gland. Urology 1982;19:653-655.

9. Chen KT, Schiff JJ. Coccidioidomycosis of prostate. Urology 1985;25:82-84.

10. Niku SD, Dalgleish G, Devendra G. Coccidioidomycosis of the prostate gland. Urology 1998;52:127.

11. Lawrence MA, Ginsberg D, Stein JP, et al. Coccidioidomycosis prostatitis associated with prostate cancer. BJU Int 1999;84:372-373.

RELATED ARTICLE: Key Points

* Coccidioidomycosis, commonly referred to as valley fever, typically presents as a self-limited respiratory infection, but may disseminate to any location, including the genitourinary tract.

* Coccidioidomycosis prostatitis should be considered in patients presenting with a prostate nodule or sterile pyuria who have resided in or traveled to the southwestern United States.

* The diagnosis of Coccidioides immitis infection of the prostate is established by prostate biopsy, and treatment consists of antifungal agents such as fluconazole or amphotericin B.

April A. Truett, MD, and Nancy F. Crum, MD, MPH

From the Infectious Diseases Division, Naval Medical Center San Diego, San Diego, CA.

The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government.

Reprint requests to April A. Truett, MD, Clinical Investigation Department (KCA), Naval Medical Center San Diego, 34800 Bob Wilson Drive, Suite 5, San Diego, CA 92134-1005. Email: aatruett@nmcsd.med.navy.mil
COPYRIGHT 2004 Southern Medical Association
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2004, Gale Group. All rights reserved. Gale Group is a Thomson Corporation Company.

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Title Annotation:Case Report
Author:Crum, Nancy F.
Publication:Southern Medical Journal
Date:Apr 1, 2004
Words:2433
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