SARS-Cov-2 Infection Uncovering Latent Mycobacterium Leprae Infection

As the number of coronavirus disease 2019 (COVID-19) cases rise globally, more information is being brought to light regarding the relationship between COVID19 and leprosy. There are very few reports of leprosy with concurrent COVID-19. Limited literature suggests two theories have been postulated thus far: (1) COVID-19 infection may trigger a leprosy reaction; and (2) leprosy treatment may cause patients to experience a severe manifestation of COVID-19 infection.


SARS-Cov-2 Infection Uncovering Latent Mycobacterium Leprae Infection
Christopher Mancuso, DO, MHS 1  As the number of coronavirus disease 2019 (COVID-19) cases rise globally, more information is being brought to light regarding the relationship between COVID-19 and leprosy. There are very few reports of leprosy with concurrent COVID-19. 1 Limited literature suggests two theories have been postulated thus far: (1) COVID-19 infection may trigger a leprosy reaction; and (2) leprosy treatment may cause patients to experience a severe manifestation of COVID-19 infection. 1,2 Also known as Hansen's disease, leprosy is a chronic granulomatous infection caused by the bacteria Mycobacterium leprae that spreads via respiratory droplets. 3 Leprosy involves immune factors, such as interleukins (IL) 4, 5, 6, 10, 13, that COVID-19 may activate or exacerbate. 4,5 In addition, infections and stress are thought to be triggers for leprosy reactions. 6 While early diagnosis and treatment with antibiotics and anti-inflammatory medications can cure an individual with leprosy, it may create susceptibility to COVID-19 by changing a patient's cytokine profile. 1,5,7,8 Despite the current social distancing mandates to prevent acquisition of COVID-19, many patients with leprosy are a part of lower socioeconomic groups associated with overcrowded living and poor sanitary conditions. 1,3 Combined with the historical shame and discrimination that leprosy patients experience, this creates major vulnerability in this patient population. 1,3,6 We present a case of newly diagnosed leprosy post-COVID-19 infection in a middleaged male. To our knowledge, this is the first reported case of its kind in the United States.

CASE REPORT
A 46-year-old Fitzpatrick VI, African-American man with a significant past medical history of recent COVID-19 infection in April 2020 presented to the dermatology clinic on July 2, 2020 with a three-week history of a rash on his face. The patient reported that he migrated from Guyana three years ago and did not have a history of or exposure to leprosy. Of note, the patient did admit to an increased amount of stress amidst the COVID-19 pandemic. On physical examination, the patient had multiple edematous and erythematous plaques of his forehead, periocular areas, nose, malar cheeks, and temples; forming the classical leonine facies (Figure 1). Patient admitted to hyperesthesia of the upper extremities without pruritus. A 3mm punch biopsy was performed on a plaque of the patient's left upper cheek. The biopsy was reported as multibacillary leprosy with innumerable beaded or fragmented organisms ( Figure 2). The patient was started on Clofazimine 50mg daily and Rifampin 600mg daily, and sent for glucose-6-phosphate dehydrogenase (G6PD) deficiency testing before starting Dapsone 100mg daily. Infectious disease was consulted for further management and the Health Department was notified.
COVID-19 is a viral respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in Wuhan, China in December 2019. The spectrum of disease caused by COVID-19 ranges from asymptomatic to SARS. 7 As the number of cases increase worldwide, clinicians realize that patients with COVID-19 may experience various coinfections. Presently, knowledge regarding co-infection with leprosy is sparse, but a few theories have been proposed.
Leprosy is a chronic granulomatous infection that leads to various cutaneous manifestations. 3 3,4,5 This form demonstrates impaired immunity due to IL-4, IL-10, and TGF-β secretion, causing large numbers of bacilli and destruction of peripheral nerves, skin, mucosa, and bones. 3,4,5 Type 2 reactions, which include erythema nodosum leprosum, are associated with immune complex deposition and neutrophil infiltrate. 3 It has been suggested that microbial infections and stress are triggers for leprosy reactions. The literature has shown SARS-CoV-2 to influence neutrophil infiltration, eventually creating hyperinflammation or cytokine storm syndrome in a number of COVID-19 cases. 2,4,9,10 Limited studies proposed two theories to explain the relationship between leprosy and COVID-19.  B.

DISCUSSION
The first theory states that COVID-19 is a risk factor for triggering a leprosy reaction due to its effect on various immunologic events. Type 1 leprosy involves multiple cytokines, therefore COVID-19 infection may trigger a Type 1 leprosy reaction due to its ability to induce secretion of similar cytokines. Type 2 leprosy is known to be associated with dermal neutrophil infiltrate, leading to skin disfiguration. SARS-CoV-2 also induces extensive neutrophil infiltrate, specifically in the pulmonary capillaries, that eventually enters circulation. 1,9,10 Increased circulating neutrophils influenced by SARS-CoV-2 may potentiate or exacerbate a Type 2 leprosy infection, as well as hasten or worsen clinical course. 2 Overall, this first theory suggests that COVID-19 may trigger lepromatous reactions.
The second theory proposes that leprosy patients undergoing active treatment with anti-inflammatory medications are at an increased risk of acquiring severe manifestations of COVID-19. 1,7 Specifically, Type 1 leprosy is treated with prednisone, and Type 2 leprosy is treated with thalidomide. 1,5 Both drugs interfere with the host's inflammatory response and create a dose-dependent immunosuppressed state. 8 There is concern that patients being treated for leprosy are vulnerable to a severe clinical manifestation of COVID-19, such as SARS. 1,7,8 There is also conflicting literature that suggests immunosuppressed patients may instead be protected. 7 Currently, more large-scale studies must be done to state with confidence how immunosuppressives impact the acquisition and clinical course of COVID-19. Although this theory does not relate to our case directly, it is an important consideration for the management of leprosy patients during the pandemic.
Leprosy reactions may be triggered by stress and infections, and the COVID-19 pandemic has caused significant emotional and psychological stress on patients. 6 When considering this and the two theories proposed, our unique case suggests that COVID-19 may induce or exacerbate leprosy reactions. 4 Leprosy reactions may lead to disfiguring complications and social isolation in a vulnerable patient population, therefore early diagnosis and treatment is necessary to minimize detrimental complications. 6 Throughout the pandemic, dermatologists must increase their index of suspicion for uncommon cases due to the possibility of COVID-19 triggers.