In Search for Equilibrium: Immunosuppression Versus Opportunistic Infection

Abstract

Post-transplant immunosuppression is necessary to prevent organ rejection. Immunosuppression itself can introduce complications arising from opportunistic infections. We present a case of disseminated blastomycosis manifested only as a skin lesion in an asymptomatic patient post-orthotopic heart transplantation. A 64-year-old female who had recently undergone orthotopic heart transplant for end-stage ischemic cardiomyopathy presented for a scheduled routine cardiac biopsy. The patient had no current complaints other than a crusted plaque noticed at her nasal tip. It initially manifested 6 months after surgery as a pimple that she repeatedly tried to manipulate resulting in redness and crust formation. Her immunosuppressive and prophylactic medications included: mycophenolate, tacrolimus, prednisone, bactrim, acyclovir, valganciclovir, pyrimethamine/sulfadiazine, and fluconazole. On physical examination, she was flushed, with a large and exquisitely tender crusted necrotic lesion involving almost the entire half of the nose anteriorly, the left forehead and right side of the neck. She had decreased air entry over the right lung field as well. A computed tomography (CT) image of the chest was ordered to investigate this concerning physical exam finding in the post-transplant state of this patient on immunosuppressive therapy. Chest CT revealed bilateral nodular pulmonary infiltrates with confluence in the posterior right upper lobe. Blood cultures for aerobic and anerobic organisms were negative. Both excisional biopsy of the nasal cutaneous ulcer and bronchial biopsy demonstrated numerous fungal yeast forms morphologically consistent with Blastomyces. Cultures of both specimens grew Blastomyces dermatitidis, with methicillin-resistant Staphylococcus aureus (MRSA) superinfection of the nose. She received 14 days of intravenous (IV) amphotericin B for disseminated blastomycosis and 7 days of IV vancomycin for MRSA. Her symptoms and cutaneous lesions improved and she received maintenance itraconazole treatment for 1 year. This case illustrates a delicate balance that must be struck between suppressing the immune response to prevent graft rejection and avoiding over-immunosuppression that can lead to susceptibility to infection. Thus, in any post-transplant patient, a vigorous history and physical must be performed given that infections may present without symptoms and cause grave consequences.

Clinical Characteristics and Outcomes of Endemic Mycoses After Solid Organ Transplantation: A Comprehensive Review

“…A total of 268 SOT recipients with an endemic mycoses were described in 204 reports [ 4–8 , 13 , 16 , 18 , 20 , 21 , 23 , 25 , 27 , 28 , 33–37 , 40 , 42 , 45 , 46 , 48–52 , 55 , 58–61 , 64–70 , 72–88 , 90–99 , 101–146 , 148–168 , 170–183 , 186 , 188–197 , 207 , 209–244 ]. Table 1 summarizes their characteristics.…”

“…Thirty-one cases of blastomycosis were reported [ 7 , 8 , 13 , 20 , 21 , 23 , 35 , 45 , 46 , 48 , 51 , 52 , 55 , 59 , 60 , 64 , 65 , 67 , 68 , 70 , 195 , 209 , 211 , 244 ]. The majority of reports from the United States (10 of 16) were within endemic areas [ 20 , 21 , 35 , 45 , 46 , 51 , 60 , 67 , 195 , 211 ].…”

“…Thirty-one cases of blastomycosis were reported [ 7 , 8 , 13 , 20 , 21 , 23 , 35 , 45 , 46 , 48 , 51 , 52 , 55 , 59 , 60 , 64 , 65 , 67 , 68 , 70 , 195 , 209 , 211 , 244 ]. The majority of reports from the United States (10 of 16) were within endemic areas [ 20 , 21 , 35 , 45 , 46 , 51 , 60 , 67 , 195 , 211 ]. Eleven [ 8 , 13 , 23 , 35 , 48 , 52 , 64 , 65 , 68 , 70 , 209 ] had documented risk factors for disseminated infection, while this was unknown in 5 cases [ 7 , 55 , 59 , 211 , 244 ].…”

“…One patient was treated with methylprednisone for worsening graft function [ 70 ], and another had chronic cellular rejection [ 51 ]. The majority were receiving mycophenolate mofetil (MMF) (19 of 29 [65.5%]) [ 7 , 8 , 13 , 21 , 35 , 45 , 46 , 48 , 55 , 59 , 64 , 65 , 67 , 70 , 244 ].…”

“…Fever occurred in half of patients (11 of 22 [50%]) [ 7 , 8 , 20 , 21 , 23 , 35 , 51 , 64 , 65 , 195 , 209 ]. Slightly less than half had disseminated infection (15 of 31 [48.4%]) [ 8 , 13 , 23 , 35 , 45 , 51 , 52 , 60 , 64 , 67 , 68 , 211 ], followed by pulmonary infection alone (12 of 31 [38.7%]) [ 7 , 20 , 21 , 46 , 67 , 70 , 195 , 209 , 211 , 244 ] and isolated cutaneous involvement (4 of 31 [12.9%]) [ 48 , 55 , 59 , 65 ]. Sites of dissemination included skin and soft tissue (n = 8), joint (n = 2), central nervous system [CNS] (n = 5), larynx, (n = 2), liver (n = 1), spleen (n = 1), and peritoneum (n = 1).…”