Cutaneous Nocardiosis in an Immunocompromised Patient
We describe a case of a 79-year-old man with chronic lymphocytic leukemia (CLL) who presented with ataxia; falls; vision loss; and numerous mobile erythematous nodules on the chin, neck, scalp, and trunk. Computed tomography of the head and chest revealed cavitary lesions in the brain and lungs. Clinically, the skin nodules were believed to represent an infectious process. Two punch biopsies were obtained, which revealed an unremarkable epidermis with a mixed inflammatory infiltrate with abscess formation in the dermis. Gram stain highlighted gram-positive branching bacterial organisms. Similar organisms were identified in a bronchoalveolar lavage specimen. Cultures from skin and blood were positive for Nocardia. Our case serves as a reminder to clinicians and pathologists to keep a broad differential diagnosis when dealing with infectious diseases in immunocompromised patients.
Practice Points
- Clinicians should consider a broad differential when dealing with infectious diseases in immunocompromised patients.
- Primary cutaneous nocardiosis classically presents as tumors or nodules with a sporotrichoid pattern along the lymphatics. Vesiculopustules and abscesses are seen in disseminated disease, which usually involves the skin, lungs, and/or central nervous system.
- Nocardia species are characteristically gram-positive, thin rods that form beaded, right-angle branching filaments.
- When nocardiosis is in the differential, special care should be taken, as organisms can be gram variable or only partially acid fast. Gram, Grocott-Gomori methenamine-silver, and acid-fast staining may be essential to making the diagnosis.
Association With CLL
Chronic lymphocytic leukemia is associated with profound immunodeficiency caused by quantitative and qualitative aberrations in both innate and adaptive immunity. This perturbation of the immune system predisposes the patient to infection.11,12 Early in the course of CLL, a patient develops neutropenia, which predisposes to bacterial infection; later, the patient develops a sustained B- and T-cell immunodeficiency that predisposes to opportunistic infection.13 Treatment-naïve patients with CLL are commonly diagnosed with respiratory and urinary tract infections.12 Chronic lymphocytic leukemia patients treated with alemtuzumab or purine analogs have been reported to have the highest risk for major infection.14
Ibrutinib is a commonly used treatment of CLL because it induces apoptosis in B cells, which are abnormal in CLL. Ibrutinib functions by inhibiting the Bruton tyrosine kinase pathway, which is essential in B-cell production and maintenance.15 Studies have reported a high rate of infection in ibrutinib-treated CLL patients14,16; salvage ibrutinib therapy has been associated with higher infection risk than primary ibrutinib therapy.16,17 Long-term follow-up studies have shown a decreased rate of infection in ibrutinib-treated CLL after 2 years or longer of treatment, suggesting a reconstitution of normal B cells and humoral immunity with longer ibrutinib therapy.16,17
Many infections have been identified in association with ibrutinib therapy, including invasive aspergillosis, disseminated fusariosis, cerebral mucormycosis, disseminated cryptococcosis, and Pneumocystis jirovecii pneumonia.18-22 Disseminated nocardiosis has been reported in a few patients with CLL, though the treatment they received for CLL varied from case to case.23-25
Identification and Treatment
Clinical and microscopic identification of Nocardia organisms can be exceedingly difficult. Primary cutaneous nocardiosis clinically presents as tumors or nodules that often have a sporotrichoid pattern along the lymphatics. In disease that disseminates to skin, nocardiosis presents as vesiculopustules or abscesses. The biopsy specimen most often shows a dense dermal and subcutaneous infiltrate of neutrophils with abscess formation. Long-standing lesions might show chronic inflammation and nonspecific granulomas.
The appearance of Nocardia organisms is quite subtle on hematoxylin and eosin staining and can be easily missed. Special stains, such as Gram and Grocott-Gomori methenamine-silver stains as well as stains for acid-fast organisms, can be invaluable in diagnosing this disease. Biopsy in immunocompromised patients when nocardiosis is part of the differential diagnosis requires extra attention because the organisms can be gram variable and only partially acid fast, as was the case in our patient. Organisms typically will be positive with silver stains.
Trimethoprim-sulfamethoxazole typically is the first-line treatment of nocardiosis. Although prognosis is excellent when disease is confined to skin, disseminated infection has 25% mortality.8 Diagnosticians should maintain a high index of suspicion for the disease, especially in immunocompromised patients, because clinical and imaging findings can be nonspecific.
Conclusion
Our patient’s primary risk factor for nocardiosis was his immunocompromised state. In addition, he was an avid gardener, which increased his risk for exposure to the microorganism. Given the timing of disease progression, our case most likely represents primary cutaneous nocardiosis with dissemination to brain, lungs, and other organs, leading to death, and serves as a reminder to dermatologists and pathologists to establish a broad differential diagnosis when dealing with an infectious process in immunocompromised patients.
