sign in sign up
<<
Home , Borderline leprosy, Erythema, Erythema nodosum, Lepromatous leprosy, Leprosy

Lepromatous with Nodosum Leprosum Presenting as Chronic Ulcers with : A Case Report and Discussion Anny Xiao, DO,* Erin Lowe, DO,** Richard Miller, DO, FAOCD***

*Traditional Rotating Intern, PGY-1, Largo Medical Center, Largo, FL ** Resident, PGY-2, Largo Medical Center, Largo, FL ***Program Director, Dermatology Residency, Largo Medical Center, Largo, FL

Disclosures: None Correspondence: Anny Xiao, DO; Largo Medical Center, Graduate Medical Education, 201 14th St. SW, Largo, FL 33770; 510-684-4190; [email protected]

Abstract Leprosy is a rare, chronic, granulomatous infectious with cutaneous and neurologic sequelae. can be a challenging differential diagnosis in dermatology practice due to several overlapping features with rheumatologic disorders. Patients with leprosy can develop reactive states as a result of -mediated inflammatory processes, leading to the appearance of additional cutaneous that may further complicate the clinical picture. We describe a case of a woman presenting with a long history of a recurrent bullous with chronic ulcers, with an evolution of vasculitic diagnoses, who was later determined to have with reactive leprosum (ENL).

Introduction accompanied by an intense bullous purpuric rash on management of sepsis secondary to bacteremia, Leprosy is a slowly progressive disease caused by bilateral arms and face. For these complaints she was with lower-extremity as the suspected with leprae (M. leprae). seen in a Complex Medical Dermatology Clinic and source. A skin was taken from the left thigh, Spread continues at a steady rate in several endemic clinically diagnosed with cutaneous polyarteritis and histopathology showed epidermal ulceration countries, with more than 200,000 new cases nodosa. The patient declined recommendations with underlying septal and lobular reported globally each year.1 Transmission occurs for further immunosuppressive therapies. The rash (Figure 3). A skin culture was positive for moderate through nasal or oral droplets in a susceptible on her arms and face ultimately resolved without growth of (S. aureus). A skin person.2 Organisms mainly infect the skin, treatment. She began attending a weekly wound smear revealed many acid-fast bacilli (AFB), and peripheral nerves, mucosal surfaces of the upper clinic for her chronic lower-extremity ulcers. an AFB stain was positive for numerous organisms , and eyes. The clinical severity of within the subcutis and (Figure 4). Other past medical history included type 2 diabetes leprosy is dependent on the affected individual’s mellitus, , arthritis, chronic On hospital day three, the patient developed degree of immunity to M. leprae, as it is hypothesized sinusitis, and bilateral iritis. The patient was born a palpable purpuric rash on bilateral upper that most immunocompetent people in endemic in Mexico and moved to northern California in extremities, trunk, and face, which subsequently areas have mounted an immune response against 2 1994. There was no recent travel, and she last visited became edematous and formed confluent flaccid it. Sequelae of this disease include deformity of the 2 Mexico 10 years prior. bullae (Figure 5). The rash was non-tender and extremities due to complications of neuropathy. non-pruritic. It was similar to her past widespread If diagnosed in a timely manner, leprosy can be On examination, the patient was febrile, rash. A skin biopsy was taken from the left arm, effectively cured with multidrug therapy before hypotensive, tachycardic, and tachypneic. Her revealing leukocytoclastic vasculitis (Figure 6). disability develops. bilateral lower extremities had multiple ulcerative The AFB smear and stain were again positive for lesions ranging from 1 cm to 5 cm, with purulent ENL, a type 2 leprosy reaction, is a severe multi- drainage and surrounding erythema (Figures 1, 2). system immune-mediated complication of Surrounding skin was warm and dry, with areas of lepromatous leprosy and that scarring and scaling. Interestingly, it was noted that causes patients to become acutely ill with fever, 3 the patient’s eyebrows were lacking hair bilaterally. , and tender erythematous skin lesions. It Laboratory studies showed leukocytosis, anemia, affects approximately half of lepromatous leprosy and lactic acidosis. The patient was admitted for cases, can involve many organ systems, and can be recurrent. ENL typically occurs in lepromatous patients with abundant bacilli in cutaneous and peripheral nerve lesions within a few years of initiating antibiotic treatment for leprosy.4 The pathophysiology has not been fully elucidated but is thought to be due to cellular immunity mechanisms and antigen-antibody immune-complex deposition Figure 2. Chronic ulcers affecting the soles of in vascular endothelium.4 the feet. Case Report A 62-year-old Hispanic woman presented to the emergency department with nausea and vomiting. Her past medical history was significant for recurrent bilateral lower-extremity ulcers, which she had been battling for seven years. The ulcers began as on bilateral thighs. Initial cutaneous biopsy revealed features of leukocytoclastic vasculitis and panniculitis. She was treated with a short course of prednisone, and the blisters improved. In subsequent years, the rash relapsed several times, and a full rheumatologic evaluation led to the diagnosis of cutaneous cryoglobulinemic vasculitis. The patient started rituximab infusions, which were discontinued after 18 months because of worsening lower-extremity ulcerating wounds. She eventually Figure 1. Chronic lower extremity ulcers upon Figure 3. H&E (2x): Biopsy of left thigh developed a secondary lower-extremity cellulitis presentation to the emergency department. showing epidermal ulceration and panniculitis.

LEPROMATOUS LEPROSY WITH ERYTHEMA NODOSUM LEPROSUM PRESENTING AS CHRONIC ULCERS WITH VASCULITIS: A CASE REPORT AND DISCUSSION numerous AFB organisms (Figure 7). The patient’s absent eyebrow hair provided a diagnostic clue, bacteremia and cellulitis resolved with 14 days of as can be a distinguishing feature of intravenous treatment. The purpuric leprosy.8 Because there are no serological tests to rash evolved into confluent erosions and ulcerations diagnose leprosy, the gold standard for diagnosis by the day of discharge (Figure 8). is skin biopsy for histological evaluation.9 PCR testing on skin biopsy to identify M. leprae DNA is Both skin obtained during this highly sensitive and specific, making it useful when hospitalization were sent to the National Hansen’s clinical or histologic features are inconclusive.10 Disease Laboratory for further evaluation with Fite stain and PCR testing for M. leprae DNA. The skin biopsy obtained from our patient’s chronic The thigh skin biopsy (hospital day one) revealed ulcers revealed features consistent with lepromatous chronic inflammatory infiltrate and numerous acid- leprosy, which is characterized by collections of fast organisms within histiocytes and endothelial diffusely distributed in the dermis cells, consistent with lepromatous leprosy. The arm with scattered or clumped lymphocytes and plasma skin biopsy (hospital day three) was significant for cells, along with numerous AFB present within 11 Figure 7. AFB (100x): Biopsy of left arm acute and chronic inflammatory infiltrate, vasculitis, cells. The diagnostic criteria for leprosy is based fibrin clots in blood vessels, and acid-fast organisms exhibiting M. leprae organisms in the cell wall. within histiocytes and endothelial cells, indicative of reactional ENL. Polymerase chain reaction (PCR) was positive for M. leprae DNA, confirming the diagnosis of active lepromatous leprosy.

The patient was subsequently referred to the National Hansen’s Disease Ambulatory Care Clinic in California for initiation of treatment. She was started on 100 mg daily, rifampin 300 mg monthly, and 50 mg daily plus an additional 300 mg once a month. She was also started on a prednisone taper for Figure 8. Large confluent ulcerations on the arm one month and 300 mg daily for treatment of the erythema nodosum leprosum six weeks after eruption of the second purpuric reaction. The patient demonstrated expeditious rash on the upper extremities and face. response to treatment. Within six weeks, almost Figure 4. AFB (100x): Biopsy of left thigh all of her skin lesions had healed with residual highlighting numerous M. leprae organisms. hyperpigmented scar tissue and scattered eschar (Figures 9, 10). She reported feeling better than she had felt in years. Discussion The clinical manifestations of leprosy depend on the host response to M. leprae. Therefore, lepromatous disease can present with a multitude of symptoms ranging from skin lesions to nerve damage. For this reason, diagnosis can be challenging. In non- endemic countries, the diagnosis of leprosy is frequently delayed, and patients may present to a variety of specialists for help.5 In the United States, where there are approximately 200 reported leprosy cases per year, one study found that leprosy patients Figure 5. Acute purpuric rash that developed experienced an average of one year of symptomatic on upper extremities on day three of 6 illness before diagnosis was made. Patients with hospital admission. leprosy have been most commonly misdiagnosed with diabetic neuropathy, , vulgaris, and numerous rheumatologic .6

Leprosy shares several common features with chronic inflammatory rheumatologic disease and can be a challenging mimicker to expose. Autoantibodies such as and Figure 9. Leg after six weeks of multi- anti-nuclear antibody are often falsely positive drug treatment, with healed scars and in leprosy.7 The patient in our case underwent residual . extensive rheumatologic evaluation and was diagnosed initially with cryoglobulinemic vasculitis, then polyarteritis nodosa. However, her skin lesions progressively worsened on rituximab immunosuppressive therapy due to the underlying undiagnosed infection.

The positive AFB smear obtained during hospitalization widened the differential diagnosis to include cutaneous caused by mycobacterial , including (M. or M. bovis), Buruli Figure 10. Arm lesion six weeks after multi- (M. ulcerans) and lepromatous leprosy or Figure 6. H&E (4x): Biopsy of left arm showing drug treatment, with healed scars and minimal erythema nodosum leprosum (M. leprae). The leukocytoclastic vasculitis. scattered eschar.

XIAO, LOWE, MILLER on the presence of one or more of the cardinal signs: References 17. Schmiedel S, Ehrhardt S, Moll I, Burchard GD. hypopigmented or reddish patches with definite 1. Naaz F, Mohanty PS, Bansal AK, Kumar D, Gupta A Thai patient with generalised inflammatory skin loss of sensation, thickened peripheral nerves, and disease 18 years after migration to . Lancet. 12 UD. Challenges beyond elimination in leprosy. Int J AFB on skin smears or biopsy. The skin lesions Mycobacteriol. 2017 Jul-Sep 1;6(3):222-8. 2006 Apr 29;367(9520):1458. are commonly macules or plaques and seldom 12 or nodules. Our patient’s presentation was 2. Walker SL, Lockwood DN. The clinical and 18. Van Veen NH, Meima A, Richardus JH. atypical in that her skin lesions had formed chronic, immunological features of leprosy. Br Med Bull. The relationship between detection delay and non-healing ulcers as a result of the prolonged 2006 Jan 1;77(1):103-21. impairment in leprosy control: a comparison of duration of her untreated disease and her comorbid patient cohorts from Bangladesh and Ethiopia. diabetes mellitus, which likely contributed to her 3. Walker SL, Balagon M, Darlong J, Doni SN, Hagge Leprosy Rev. 2006 Dec 1;77(4):356. impaired wound healing and the recurrent infection 13 DA, Halwai V, John A, Lambert SM, Maghanoy A, of chronic wounds. Nery JA, Neupane KD. ENLIST 1: An International Multi-centre Cross-sectional Study of the Clinical The biopsy from the purpuric rash that developed Features of Erythema Nodosum Leprosum. PLoS acutely on hospital day three was histologically Negl Trop Dis. 2015 Sep 9;9(9):e0004065. consistent with ENL. ENL is distinguished by intense perivascular infiltrates of neutrophils 3 4. Scollard DM, Adams LB, Gillis TP, Krahenbuhl throughout the dermis and subcutis. Other JL, Truman RW, Williams DL. The continuing characteristic histological features include challenges of leprosy. Clin Microbiol Rev. 2006 Apr tissue edema, inflammatory infiltrates, 1;19(2):338-81. vasculitis, necrotizing changes and thrombus 11 formation within vessels. The appearance of 5. Lockwood DN, Reid AJ. The diagnosis of leprosy ENL is classically described as crops of tender is delayed in the United Kingdom. QJM. 2001 Apr subcutaneous nodules on the face and outer 1;94(4):207-12. surfaces of limbs.9 Our patient had purpuric, bullous lesions on her face and arms. Atypical 6. Leon KE, Jacob JT, Franco-Paredes C, Kozarsky presentations of ENL, documented in case PE, Wu HM, Fairley JK. Delayed Diagnosis, reports from high-endemic countries such as Leprosy Reactions, and Nerve Injury Among Mexico and India, include bullous, ulcerated, Individuals With Hansen’s Disease Seen at a pustular, and -like United States Clinic. Open Forum Infect Dis. 2016 lesions.14,15 ENL can present as Mar 25;3(2):ofw063. affecting multiple systems, causing iritis, , myositis, lymphadenitis, and arthritis.16 It 7. Salvi S, Chopra A. Leprosy in a may occur as a single acute episode or have a setting: a challenging mimic to expose. Clin protracted relapsing course lasting several years.16 Rheumatol. 2013 Oct 1;32(10):1557-63. Our patient had a history of iritis and arthritis, which may have been the sequelae of recurrent 8. Krishnan A, Kar S. Bilateral madarosis as the ENL. Similarly, her prior diagnoses of peripheral solitary presenting feature of multibacillary leprosy. neuropathy and chronic sinusitis were likely Int J Trichology. 2012 Jul;4(3):9. manifestations of lepromatous disease. 9. Britton WJ, Lockwood DNJ. Leprosy. Lancet First-line treatment for ENL is immunosuppression 2004; 363:1209–19. with .3 Another highly effective agent is thalidomide, which treats the acute inflammation 10. Williams DL, Scollard DM, Gillis TP. PCR- and maintains long-term immunosuppression with based diagnosis of leprosy in the United States. few side effects.3 Clin Microbiol Newsl. 2003 Apr 15;25(8):57-61. Conclusion 11. Massone C, Belachew WA, Schettini A. Leprosy can be difficult to diagnosis in regions Histopathology of the lepromatous skin biopsy. where the is low. For patients from Clin Dermatol. 2015 Feb 28;33(1):38-45. endemic countries, it is important to place the diagnosis high on one’s differential. Because the 12. Eichelmann K, González SG, Salas-Alanis of leprosy averages four years JC, Ocampo-Candiani J. Leprosy. An update: to ten years, patients can present with leprosy long definition, pathogenesis, classification, diagnosis, after leaving an endemic area.17 Early diagnosis and treatment. Actas Dermosifiliogr (English and treatment of leprosy and lepromatous Edition). 2013 Sep 30;104(7):554-63. reactions is essential for minimizing nerve damage, preventing disability, and effectively curing the 13. Greenhalgh DG. Wound healing and diabetes disease. Neuropathic impairment and morbidity mellitus. Clin Plast Surg. 2003 Jan 31;30(1):37-45. worsens with delayed time to diagnosis, resulting in 14. Petro TS. Bullous type of reaction mimicking complications such as contractures and secondary 18 in lepromatous leprosy. Indian J damage to neuropathic areas. Diagnosing leprosy Leprosy. 1996;68(2):179-81. thus requires a high index of clinical suspicion and astute clinical judgment. This uncommon but 15. Pocaterra L, Jain S, Reddy R, Muzaffarullah debilitating disease should remain in consideration S, Torres O, Suneetha S, Lockwood DN. Clinical in the differential diagnosis of a patient presenting course of erythema nodosum leprosum: an 11-year with chronic and neuropathy, even in cohort study in Hyderabad, India. Am J Trop Med non-endemic regions. Hyg. 2006 May 1;74(5):868-79.

16. Tewari R, Nijhawan VS, Mishra MN, Srinivasan S, Chattwal PK, Satyanarayana S. An unusual presentation of type 2 lepra reaction: role of fine needle aspiration cytology. Acta Cytologica. 2008;52(6):743-5.

LEPROMATOUS LEPROSY WITH ERYTHEMA NODOSUM LEPROSUM PRESENTING AS CHRONIC ULCERS WITH VASCULITIS: A CASE REPORT AND DISCUSSION