If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
Corresponding author: Michael G. Galvez, MD, Division of Plastic and Hand Surgery, Pediatric Hand and Upper Extremity Surgery, Department of Infectious Disease, Valley Children’s Hospital Healthcare: Valley Children’s Hospital, 9300 Valley Children’s Place GE07, Madera, CA 93636.
Disseminated coccidioidomycosis is a rare cause of flexor tendon tenosynovitis, particularly in the pediatric population. We present the case of a 2-month-old male infant with disseminated coccidioidomycosis of the right index finger, which was initially treated with debridement and long-term antifungal therapy. Six months after discontinuing antifungal medications and at the age of 2 years, the patient presented with relapse of coccidioidomycosis of his right index finger. Serial debridement and long-term antifungal therapy resulted in disease quiescence. The relapse of pediatric coccidioidomycosis tenosynovitis using surgical management with accompanying magnetic resonance imaging, histopathology, and intraoperative findings is described herein. Coccidioidomycosis should be considered for the differential diagnosis of pediatric patients who have traveled to or live in endemic areas and present with indolent hand infections.
Coccidioidomycosis is an infection caused by a fungus of the genus Coccidioides (eg, Coccidioides immitis and Coccidioides posadasii). Also known as Valley Fever, Coccidioides species are commonly found in the southwestern United States. The San Joaquin Central Valley (SJCV) in Central California is a well-known geographic locus for Coccidioides species. Since 1979, multiple areas along the SJCV have reported coccidioidomycosis outbreaks among workers.
Coccidioidomycosis infections are categorized into the following 2 forms: (1) pulmonary and (2) systemic dissemination. Most infected individuals remain asymptomatic, however some patients develop a self-limited flu-like illness or community-acquired pneumonia.
Risk factors for systemic disease include infants aged <1 year, pregnant patients, immunocompromised patients, patients with elevated complement serum titers of immunoglobulin G (IgG) or IgM less than or equal to 1:16, and diabetics.
Diagnosis is typically made by at least 1 of the following findings: (1) positive Coccidioides immunodiffusion, (2) complement fixation (CF) serology, (3) a body specimen culturing Coccidioides, or (4) tissue pathology demonstrating Coccidioides spherules.
Complement fixation titer is a quantitative laboratory measure of the severity of the infection. It is also used to assess the infection’s responsiveness to treatment and disease progression. A coccidioidal titer of over 1:16 indicates disseminated infection. After adequate surgical source control, antifungal therapy goals include the clinical quiescence of symptoms and a lower CF titer.
In this article we report an infant presenting with disseminated coccidioidomycosis with relapse affecting the flexor tendons. His treatment required serial debridement and long-term antifungal therapy. The diagnostic evaluation and medical treatment for this patient have been previously reported in case series of pediatric coccidioidomycosis in the SJCV.
In this article, we will focus on the imaging, gross pathology, pathology, and surgical management of coccidioidomycosis infections of the hand. Written informed consent was obtained from guardian for publication of this case report and accompanying images.
Case Report
Initial presentation
A 2-month 22-day–old male infant without significant medical history presented with right index digit erythema and swelling. Three weeks before the presentation, the patient’s guardian had accidentally bumped his finger while swaddling him. The patient resided in the SJCV region in Central California. On examination, there was mild erythema of the proximal phalanx and diffuse swelling of the finger. The volar soft tissues of all 3 phalanges were indurated and firm to palpation. The patient could not demonstrate any gross flexion of the proximal interphalangeal joint. Radiographs demonstrated lytic changes to the proximal phalanx of the index digit. Magnetic resonance imaging (MRI) demonstrated a lobulated soft tissue mass around the flexor tendon sheath extending from the middle of the second metacarpal to the distal fingertip (Fig. 1). Serum enzyme immunoassay result was IgG positive. Moreover, the patient had bilateral pulmonary nodules with associated mediastinal lymphadenopathy (on the basis of computed tomography findings).
Figure 1Axial MRI T1 sequences demonstrating an increasing lesion involving the flexor tendons in the A metacarpophalangeal and B proximal interphalangeal joint at the age of 2 months.
Within 24 hours, the patient underwent excisional biopsy of his right second-digit flexor tendon sheath. No definitive lesion was encountered during this biopsy. However, histopathology revealed spherules with endosporulation consistent with coccidioidomycosis. Results for coccidioidal immunodiffusion antibody were positive for IgG and the CF titer was 1:256. He was placed on intravenous liposomal amphotericin B at 5 mg/kg/d. Tissue cultures grew C. immitis or C. posadasii. Due to worsening respiratory symptoms, liposomal amphotericin B was changed to intravenous voriconazole, caspofungin, and steroids on the 42nd day of admission. With continued swelling of the hand, the patient had a second debridement of his index finger. He was discharged after 121 days of hospitalization on oral voriconazole (80 mg twice daily), which was later changed to oral fluconazole (220 mg daily). His disseminated disease resolved. Once the patient showed clinical improvement with no infection on his hand examination and low stable coccidioidal CF titers, fluconazole was discontinued after 19 months. The patient was followed up closely every 2 months with serial examinations with CF titers and the guardian was instructed to report any increased swelling, pain, or erythema.
Relapse
Twenty-five months after the initial biopsy and 6 months after discontinuing antifungal therapy, the then 2-year 4-month–old patient presented with right radial palmar swelling that suggested the recurrence of coccidioidomycosis flexor tendon involvement (Fig. 2). There was a large mass volar to the flexor pulleys within the palm and index finger, as demonstrated on MRI images and during surgery (Figs. 3 and 4). He underwent aggressive tenosynovectomy with debridement and excision of A1 and A2 pulleys of the second ray given significant infiltration of the lesion (Fig. 5). The flexor digitorum superficialis and flexor digitorum profundus (FDP) tendons did not demonstrate infectious mass infiltration. The FDP tendon was observed to insert aberrantly onto the proximal phalanx base, most likely secondary to rupture and subsequent scarring from the initial infection. In addition, there was a tenodesis across the distal aspect of the distal interphalangeal joint from the FDP tendon. Pathologic examination demonstrated spherules containing endospores, which confirmed coccidioidomycosis (Fig. 6). He underwent a planned second exploration and debridement because of the extensive soft tissue involvement found in his first operation, with findings of rim of tissue necrosis that was debrided. The previous scar from the initial debridement was linear, and therefore, a Z-plasty was performed to lengthen the scar (Fig. 7). After his 2 surgeries he healed well without recurrence. He has not had a recurrence (Fig. 8) after being maintained on a prolonged course of antifungal therapy (fluconazole) for 3 years after this relapse. He was monitored 4 times per year with coccidioidal CF titers, a liver panel to determine hepatotoxicity, and an MRI every 12 months. The MRI was conducted because of the concern regarding relapse. He did not regain active flexor tendon function of his index finger distal to zone 2. However, he could lay his hand flat on a table and make a full fist with compensation from his long finger to passively flex his index finger into the palm. The patient’s guardian decided against further staged reconstruction.
Figure 2Right thenar hand swelling that suggested the recurrence of coccidioidomycosis with previous linear scar.
Figure 3Axial MRI T1 sequences demonstrating an increasing lesion involving the flexor tendons in the A metacarpophalangeal and B proximal interphalangeal joint at the age of 2 years 4 months.
Figure 4A Infiltrative mass overlying both flexor digitorum tendons and B with macro photography. There was involvement of the A1 and A2 pulleys of the second ray.
Figure 6Sections show fibrocollagenous and fibro-adipose tissue containing abundant mixed inflammation and necrotizing granulomas. Spherules containing endospores pathognomonic for Coccidioides were identified within the necrotizing granulomas. (A Hematoxylin-eosin stain; B Grocott methenamine silver stain; 40× magnification).
Figure 8A Healed incision after repeat debridement at 2-year follow-up. B Functional ability to make a fist with the index finger with compensation from the middle finger.
In both adults and children, surgical debridement is necessary to control localized infection. Long-term antifungal therapy is necessary to prevent the relapse of symptoms.
The indolent relapsing nature of coccidioidomycosis infections has been well-reported in adult populations from medical centers in endemic areas, such as Arizona and Central California.
At least half of these patients require readmission. These statistics reflect the subacute and chronic nature of coccidioidomycosis, with similar natural history affecting patients with upper extremity involvement.
At least 2 adult cases of coccidioidomycosis of the hand have been reported as relapse after the patients resumed chemotherapy.
One of these patients had previous pulmonary involvement with coccidioidomycosis and presented with erythema and swelling in the palm. The authors of that study recognized the need for local disease control and performed a resection of the infectious mass from the flexor digitorum superficialis, FDP, and underlying skin of the second ray.
described 2 patients with recurrent coccidioidomycosis to the dorsal wrist extensors. Both resided in Arizona and had previous infections. Steroid use resulted in recurrence. The first patient received surgical debridement and antifungal therapy. However, due to pre-existing hepatic disease, antifungal therapy was discontinued for this patient, who reportedly died of hepatic disease. The second patient relapsed after 26 months despite 1 year of antifungal treatment and surgical debridement. This patient was placed on lifetime antifungal suppression.
The diagnosis of coccidioidomycosis is often delayed and can be confounding with other comorbidities such as rheumatoid arthritis, de Quervain disease, and wrist ganglion.
No risk factors of immunosuppression such as immunocompromizing drug use (steroids, chemotherapy), HIV, or diabetes were observed in our patient. Recent findings suggest that children aged <1 year or >10 years had a higher risk of extrapulmonary infections.
There are also ongoing investigations for an immunologic phenotype that predisposes patients to disseminated disease. In patients with primary immunodeficiency and disseminated coccidioidomycosis, interleukin 12, signal transducer and activator of transcription 3, and interferon gamma pathways are needed for a normal immune response against cocci.
Pediatric patients with disseminated disease may benefit from genetic consultation.
Coccidioidomycosis should be included in the differential diagnosis for atypical infections of the pediatric hand. This diagnosis is especially relevant for families residing in endemic areas, such as Arizona and California. An algorithm that recognizes the residence or travel history of a patient presenting with an indolent infectious mass should include coccidioidomycosis as a potential culprit. Delays in diagnosis often reflect the nonspecific nature of symptoms—atraumatic swelling with inconsistent erythematous skin changes. With upper extremity involvement, MRI imaging can help determine the extent of the disease. Definitive treatment should include considerations for urgent biopsy, antifungal therapy, and serial debridement, as needed. Long-term serial examinations with prolonged antifungal therapy in close collaboration with colleagues working on infectious diseases are necessary to resolve this persistent infection. Complement fixation titer should be performed and if an increase is observed along with clinical concern regarding an infection, then an MRI should be performed. In the setting of relapse after treatment, MRI can be added besides CF titers and serial exams to further ensure that there is no recurrence.
References
Wilken J.A.
Sondermeyer G.
Shusterman D.
et al.
Coccidioidomycosis among workers constructing solar power farms, California, USA, 2011-2014.
00001-4&id=gr1.jpg){kind=link}
00001-4&id=gr2.jpg){kind=link}
00001-4&id=gr3.jpg){kind=link}
00001-4&id=gr4.jpg){kind=link}
00001-4&id=gr5.jpg){kind=link}
00001-4&id=gr6.jpg){kind=link}
00001-4&id=gr7.jpg){kind=link}
00001-4&id=gr8.jpg){kind=link}