What Caused Man’s Saddle-Nose Deformity Years After Lymphoma Dx?August 1, 2022
What has caused this man to have a severely congested nose and a saddle-nose deformity for 4 months, preceded by years of widespread skin lesions? That’s the diagnostic dilemma described by Timothy Shaver, MD, of George Washington University School of Medicine & Health Sciences in Washington, D.C., and colleagues in JAMA Otolaryngology-Head & Neck Surgery.
It all began when a 66-year-old African-American man presented to the otolaryngology clinic for assessment of the significant nasal congestion he had been experiencing for several months. He told clinicians that 5 years earlier he had developed widespread raised reddish patches of skin, and his records showed that he was subsequently diagnosed with hypopigmented cutaneous T-cell lymphoma (CTCL, mycosis fungoides type).
At that time, the patient received a regimen of narrowband UV-B phototherapy and triamcinolone cream — treatment he continued for 4 years. When his symptoms worsened significantly about 4 months before he presented for evaluation, clinicians biopsied his cutaneous lesions to see if the CTCL was progressing.
Physical examination at that time revealed large ring-shaped plaques with peripheral hyperpigmentation of the body. The patient’s forehead, cheek bones, and scalp had confluent, raised pink patches of thick hardened skin with slightly raised edges. The nasal septum had an inverted V deformity with compromise of the keystone junction.
Thick mucus and synechiae formation blocked the nasal passages, almost completely obstructing the entire nasal passage bilaterally, the authors said. Clinicians diagnosed the patient as having lepromatous leprosy (also known as Hansen disease).
Leprosy/Hansen disease is a bacterial infection caused by either Mycobacterium leprae or M. lepromatosis. The bacterium is an acid-fast bacillus characterized by slow growth, with a predilection for growth within macrophages, endothelial cells, and Schwann cells, Shaver and co-authors noted. They added that while the bacterium is carried primarily by humans, nine-banded armadillos are a well-known reservoir of M. leprae within both North and South America.
In 2000, the World Health Organization (WHO) considered the disease to be eliminated, using the criterion of a decrease in prevalence to less than one infection per 10,000 individuals. “However, there continues to be approximately 200,000 cases per year worldwide, with approximately 80% of these cases occurring in India, Brazil, and Indonesia,” the case authors said.
They explained that contrary to common thinking about the disease, the vast majority of the population (95%) is actually not susceptible to infection with M. leprae, according to the National Hansen’s Disease Program of the U.S. Health Resources and Services Association. The program also states that 159 new cases were reported in the U.S. in 2020 (the most recent year for which data are available).
Similarly, CDC notes that “150 to 250 cases are reported [in the U.S.] each year, with most new cases in 2018 reported from Arkansas, California, Florida, Hawaii, Louisiana, New York, and Texas.”
Not surprisingly, risk factors for catching Hansen disease include close contact with someone who has the infection, exposure to armadillos, and immunosuppression or immunodeficiencies, the case authors noted, adding that the lepromatous form of Hansen disease appears to be more likely to develop in the presence of the HLA-DQ1 gene.
Shaver and co-authors explained that because M. leprae tends to favor cooler parts of the body — temperatures of approximately 27-30°C (81-86°F) — it flourishes on the skin and especially in the nasal mucosa, which may account for the role of respiratory droplets as the most important mode of transmission.
Leprosy has six clinical manifestations according to the Ridley-Jopling clinical classification, which includes two ends of a spectrum “determined by immunologic status with lepromatous leprosy (LL) on one end with least immunity and tuberculoid leprosy (TL) on the other with strong immunity. Borderline TL, borderline LL, mid-borderline, and indeterminate disease types constitute varying mixtures of both poles,” the case authors wrote.
In general, TL tends to elicit a vigorous immune response characterized by a few well-demarcated, anesthetic skin lesions, whereas LL is associated with a weak immune response, causing multiple lesions that can affect other organ systems.
The initial presentation of leprosy often involves development of lesions within the nasal mucosa in advance of skin manifestations, Shaver and co-authors noted. They cited one 1974 study of leprosy in 77 individuals, in which 94% reported an initial nasal symptom, “with 66% of them specifically complaining of nasal obstruction due to granulomatous lesions developing within the nasal cavity.”
As the disease progresses, it is associated with further invasion of the nasal mucosa causing ulcerations, nose bleeds, and perforations of the nasal septum, the group noted. Finally, in the later stages, the infection extends to the nerves, causing abnormal or reduced sensation, “increasing the risk of saddle-nose deformity and atrophic rhinitis.”
The WHO recommends that leprosy treatment be based on the clinical classification — i.e., patients with LL should receive rifampicin, dapsone, and clofazimine for 12 months, while those with TL should receive rifampicin and dapsone for 6 months.
When there are concerns about intolerance or severe adverse effects with these medications, an alternative regimen using ofloxacin, minocycline, and clarithromycin has been proposed, the authors noted. Reconstructive surgery is generally undertaken when the infection is no longer active, as was the case for this patient.
Despite being relatively rare in the U.S., leprosy remains an infectious disease that can cause “significant morbidity if left untreated,” Shaver and team cautioned. They urged clinicians, especially those in the field of otolaryngology, to perform a thorough workup of patients who present with nasal obstruction, recurrent epistaxis, rhinitis, and/or saddle-nose deformity.
Given that nasal symptoms are often among the initial manifestations of leprosy, “swift responsiveness and initiation of treatment may save the patient from more significant complications,” the team wrote. Identification of Hansen disease as the most likely diagnosis in this patient was informed by observations of “dyspigmented plaques with cutaneous dysesthesia, a positive Fite stain, and characteristic deformities, such as saddle-nose deformity and leonine facies,” the group noted.
Shaver and co-authors reported no conflicts of interest.