Reactivation Histoplasmosis Manifested by Lymphocutaneous Fistula with Cervical Drainage of Stones

Case Presentation

A 22-year-old female from the midwestern U.S. presented for the assessment of a tender neck lesion. Eight years earlier, she underwent a biopsy of a mass in the same location; the culture grew Histoplasma capsulatum. The patients prior physicians felt that the infection was likely to be self-limiting and did not prescribe antimicrobial therapy. The mass resolved spontaneously.

In February 2020, she developed progressively worsening pain, erythema, and swelling over a period of several weeks at the site of the prior neck mass (Figure 1). She did not have fever, weight loss, night sweats, or dysphagia. Otherwise, her past medical history was unremarkable, and there was no apparent evidence of immunosuppression. Physical examination revealed a 4 ˆ 3 cm firm, tender, erythematous non-fluctuant mass in the left lower anterior cervical area. No lymphadenopathy was noted elsewhere. Her lungs were clear. The cardiac and abdominal examinations were normal. No skin lesions were observed.

Figure 1: Left Neck Mass.

The chemistry panel and complete blood count were normal; C-reactive protein was 18.3. The neck ultrasound revealed two avascular neck soft tissue lesions, measuring 1.6 ˆ 3.0 ˆ 1.6 cm and 4.3 ˆ 4.3 ˆ 2.1 cm, respectively. Numerous tiny bright echoes, presumed to represent calcifications, were seen in both lesions (Figure 2). On the cine images, there appeared to be movement within the central portion of the lesions, suggesting a complex cystic component. Chest imaging studies were not conducted. The Histoplasma yeast complement fixation titer was 1:32, and m-band immunodiffusion was positive; the urine Histoplasma antigen (tested at Quest Laboratory ®) was negative. The HIV antibody was negative. 

Figure 2: Ultrasound of left anterior cervical region.

The patient received a loading dose of itraconazole, 200 mg tid for 3 days, and then was treated with 200 mg bid for 6 months. Eight days after the initiation of treatment, she returned to clinic when she noted spontaneous copious thick yellow neck drainage (Figure 3), which contained multiple 1–2 mm gravel-like stones (Figure 4). A fungal culture was not completed. The drainage abated within a few days without intervention, and her neck mass resolved within 3 months.

Figure 3: Caseous drainage from neck mass.

Figure 4: Photo courtesy of Brett Pruett.

Discussion

Histoplasma capsulatum is the most common endemic mycosis in the United States [1]. Although most cases are asymptomatic, disseminated infection involving the reticuloendothelial system occurs in approximately 1 in 2000 infected individuals [2]. Disseminated histoplasmosis is much more common among patients with impaired cellular immunity, in whom the infection is progressive and life-threatening, but cases also occur in persons with no known immunosuppressing conditions [2]. In immunocompetent persons, disseminated histoplasmosis can pursue an indolent course [3]. The
detection of Histoplasma antigenuria is the most sensitive diagnostic test [4]. However, false negative urine Histoplasma antigen results have been reported in patients with documented disseminated infection [5].

Conclusion

Histoplasmosis-induced lithiasis is not limited to the respiratory tract. The reactivation of latent infection appears plausible. Patients with histoplasmosis are at risk for paradoxical transiently worsening local inflammation, either in the central nervous system or elsewhere, while receiving ultimately effective antifungal therapy.

Author Contributions

All authors contributed equally to this article. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Acknowledgments

The authors thank our patient for her support of this publication.

Conflicts of Interest