A 46-year-old woman with dermatomyositis diagnosed 5 months earlier, presented with a 1-month history of pain, warmth, redness and swelling localized to the metacarpophalangeal (MCP) joints and proximal interphalangeal (PIP) joints along with limitation of the movement of fingers and wrist. There was intermittent low-grade fever, occasional night sweats and recent onset of dry cough and loose stools over the past 1 week. Medications were prednisone 60 mg per day and mycophenolate mofetil (MMF) 1500 mg twice daily for the past 4 months, with hydroxychloroquine 200 mg twice daily added 2 weeks prior due to worsening symptoms of dermatomyositis including fatigue, as well as trimethoprim/sulfamethoxazole (TMP/SMX) 800/160 mg thrice weekly for Pneumocystis jirovecii prophylaxis.
Patient was born and raised in the upper midwestern United States, married with four healthy children and worked as a corporate meeting planner. One year prior to presentation, the patient went camping and swam in a freshwater lake. There was occasional gardening prior to the diagnosis of dermatomyositis. There was no exposure to fish tanks. Travel was extensive throughout the US including Iowa, Illinois, California, Nevada, Arizona, Texas and Georgia.
On physical examination, the patient appeared well and was not in acute distress. Blood pressure was 134/80 mm Hg, heart rate 77 beats per min, respiratory rate 18 breaths per minute and temperature 36.9 C. Examination of the left upper extremity noted swelling about the ulnar aspect of the left dorsal hand. There was pain with gentle range of motion about the ulnar aspect of left wrist and fourth and fifth MCP joints; no pain was elicited with gentle passive range of motion about any of the other joints of her left hand. There was no active synovitis in other joints. Sensation to light touch was intact in the median, ulnar and radial nerve distributions. A rash consistent with dermatomyositis was present on the chest, shoulders, forearm and dorsal aspect of both hands over the MCP joints (see Fig. 1). No open wounds were seen. All other systems were within normal limits.
The white blood cell count was  (range  to ), and platelet count was  (range  to ). Sedimentation rate was 32 mm/h (range 0-29 mm/h), and c-reactive protein (CRP) was 52 mg/L (reference range  8 mg/L). Alanine aminotransferase was 77 U/L (range 7-45 U/L), aspartate aminotransferase was 28 U/L (range 28-43 U/L) and alkaline phosphatase was 51 U/L (range 37-98 U/L). QuantiFERON-TB Gold Plus was indeterminate, and human immunodeficiency virus (HIV) screen was negative. An X-ray of the chest was clear.
An ultrasound of the left hand was notable for tenosynovitis of the left fourth dorsal compartment and subcutaneous edema of her dorsal left hand. On post-contrast T1-weighted fat-suppressed magnetic resonance imaging (MRI) of the left hand, there was peripherally enhancing tenosynovitis involving the extensor compartment (Fig. 2). There was no evidence of underlying septic arthritis or osteomyelitis.
Orthopedic hand surgery was consulted. The patient underwent tenosynovectomy of the extensor tendons of the left wrist and hand along with irrigation and debridement. Upon exposing the extensor mechanism of the left hand, inflammation was noted in the fourth extensor compartment with edema and fluid but no frank pus (Fig. 3). Multiple specimens were sent for bacterial, fungal and mycobacterial cultures as well as Gram, fungal and acid-fast stains on fresh tissue.
Surgical pathology from the tenosynovium revealed fibrinous exudate and severe chronic inflammation. Gram, fungal and mycobacterial stains on fresh tissue were negative.
There was no growth on bacterial cultures. Fungal cultures revealed the growth of Histoplasma capsulatum at day six. Serology for Blastomyces, Aspergillus and Sporothrix were negative; Histoplasma serology and urine antigen were positive (Table 1). The patient was started on itraconazole 200 mg twice daily and was gradually being weaned off prednisone.
There was a good initial response to antifungal therapy and itraconazole levels were within therapeutic range. Three months following the initial left hand debridement, the patient presented with a new nodule and a 1.2 cm fluid collection on the third MCP joint of the left hand; MRI was suggestive of worsening tenosynovitis (Fig. 4).
Patient underwent additional irrigation and debridement; there was a thick rind of tissue around the extensor tendons of fourth and fifth compartments. Fungal smear of a fresh sample from the infected fluid collection showed many yeast forms; all of the fungal cultures remained negative. Surgical pathology was notable for necrotizing granulomatous inflammation but no fungal forms were noted on the surgical pathology specimens at that time. Itraconazole was continued. At 6 months after the initial debridement, the patient was weaned off steroids and mycophenolate and was started on monthly immunoglobulin therapy for dermatomyositis.
Soon after completely discontinuing steroids at 6 months of antifungal therapy, the patient presented with weeping, nodular, white lesions along the surgical incision marks (Fig. 5). Urine Histoplasma antigen as well as serologies showed improvement (Table 1). Nevertheless, there was concern about possible clinical progression of the infection while on itraconazole.
Dermatologic punch biopsy of one of these lesions revealed necrotizing granulomatous inflammation (Fig. 6) with small, budding yeasts seen on Grocott's methenamine silver (GMS) stain, consistent with Histoplasma (Fig. 7). An indium-labeled white blood cell scan did not reveal focal bone uptake in the left hand, although there was significant soft tissue uptake. The patient underwent repeat tenosynovial debridement and intraoperatively was found to have extensive inflammation and erosions of the fourth extensor compartment tendons in the dorsum of the left hand. Postoperatively, the patient was started on intravenous liposomal amphotericin B overlapped with oral delayed release posaconazole 300 mg per day. Treatment was complicated by severe electrolyte abnormalities, which prompted discontinuation of liposomal amphotericin B. Fungal cultures were negative yet again. Serum and urine Histoplasma antigen revealed stable low-level positives (see Table 1, at 6 months). There was a concern that the fistulizing tracks with tenosynovitis could represent immune reconstitution inflammatory syndrome (IRIS). In view of this, she was administered oral prednisone for suspected IRIS with a plan for a prolonged taper. TMP/SMX for Pneumocystis prophylaxis was re-started as well. After 4 weeks, posaconazole was changed back to itraconazole 200 mg twice per day due to cost issues.
At the time of the patient's last follow-up, the suppurative and ulcerative lesions on the left dorsal hand, as well as the edema, had mainly resolved, leaving indurated violaceous scars (Fig. 8). A plan for a prolonged steroid taper was proposed in the setting of probable IRIS. The anticipated duration of therapy with itraconazole was 1 year assuming that the elevated serum and urine Histoplasma antigen levels completely resolved.