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Gorgas Case 2018-03

Epidemiology: Born in Piura on the north coast of Peru, moved to Lima and has been living there for the past 50 years. No known TB contacts.

Physical Examination: BP: 110/70 mmHg. HR: 70 bpm. RR: 20 rpm. T: 37. Sat: 98 % (FiO2: 0.21). No apparent distress with clear mentation. Skin: Multiple dermal and subcutaneous nodular erythematous lesions, mobile, tender, 2 x 1.5 cm localized over the upper limbs, anterior and posterior thorax and abdomen, some of these have pustules on the top (Image A and B). Conglomeration of very painful and extremely tender nodules on both thighs. Nodules had a yellowish content. No lesions on the face. Chest: clear to auscultation bilaterally, no crackles. Cardiovascular: regular heartbeat, no murmurs. Abdomen: soft, non-distended, normal bowel sounds, not tender to palpation. Neurological: Decreased muscle strength in the right cubital territory and thickened superficial branch of the left radial nerve plus hypoesthesia in both hands and anesthesia on both feet. Cranial nerves: afferent corneal sensation decreased bilaterally.

Discussion: Smear of a pustule was taken from one nodule on the right upper arm and a Fite-Faraco stain showed a hypocellular smear composed mainly of neutrophils (red arrow) and numerous clustered bacilli (black arrow) (Image C). Additionally, a skin biopsy of a nodule from the anterior chest wall was performed, Fite-Faraco staining of a skin biopsy over a chest-wall nodule showed foam cells (black arrow) and many acid-fast bacilli (yellow arrow) (Image D).

When first seen by us 2 years earlier he presented with areas of infiltrated skin all over the body, multiple papular lesions as well as tender dermal and subcutaneous nodules on the upper limbs, thorax, abdomen and thighs characteristic of lepromatous leprosy. He was treated with a complete course of WHO multi-drug therapy (MDT) for 1year. Patients with lepromatous leprosy have no cell-mediated immunity against the bacterium, so the bacteria are always killed by 1-year of therapy but they remain in the body because these patients cannot eliminate them, they will disappear progressively over several years.

Leprosy is a disease of peripheral nerves and skin. Leprosy can be diagnosed clinically in any patient with simultaneous skin lesions and sensory loss over the lesions unless there is hyperkeratosis. Type 2 inflammatory reactions, such as seen here have as the most common presentation erythema nodosum leprosum (ENL). ENL may occur in patients prior to therapy, during therapy and/or after therapy until the antigen load decreases markedly. ENL may present as repeated acute episodes or may be chronic and ongoing. This is a systemic immune mediated disorder, associated with antigen-antibody immune-complex deposition in tissues, usually with high levels of tissue and circulating TNF-alpha.

Lepromatous patients have high levels of antibodies and high levels of antigens (bacterial load) and they produce immune complexes. ENL presents usually with many tender dermal and subcutaneous erythematous nodules that occurs in up to 50% of lepromatous leprosy cases [Am J Trop Med Hyg. 2006;74:868-79] and 25% of borderline lepromatous patients [Dermatology Online J 2006; 12:29], due to their high bacterial loads. The lesions of ENL differ from the common erythema nodosum in that the nodules occur anywhere in the body rather than on the shins, whereas in erythema nodosum they occur on the shins and rarely in other places. On the shins erythema nodosum lesions are difficult to hold, they are more plaque-like, whereas ENL lesions in other areas are easily hold as a subcutaneous nodular lesion. In addition, ENL nodules may ulcerate and drain pus, with no pyogenic bacteria but with usually dead leprosy bacilli. The PAP smear of the content of the nodules in this patient showed a hypocellular smear composed mainly of neutrophils with abundant bacilli on Fite Faraco staining (Image C). As long as patients have bacteria (antigens) they produce immune complexes and may precipitate ENL repeatedly several years after therapy. Clinically, a relapse would not be suspected in this patient, due to lack of new infiltrative areas on the skin and no new peripheral nerve involvement, so he only needs therapy for the reaction. ENL histopathology shows an infiltration by neutrophils, which is not seen in a biopsy of leprosy without type 2 reaction.

ENL may also produce to varying degrees, fever, neuritis, edema, arthralgias, leukocytosis, uveitis, dactylitis, periostitis, orchitis, lymphadenitis and nephritis. ENL may occur in patients prior to therapy (onset 4 years before therapy in this case), during therapy and/or after therapy until the antigen load decreases markedly. ENL may present as repeated acute episodes, such as in this patient, or may be chronic or ongoing.

ENL can be treated symptomatically if mild or with prednisone or thalidomide if severe. Thalidomide is the drug of choice for severe ENL as in this case and very effective for neuritis due to type 2 reaction. A dose of 300 to 400 mg daily will usually control the reaction within 48 hours. The dose is then tapered usually every 7-10 days to a maintenance level, which is generally around 100 mg daily and then attempts are made to taper off the drug. This patient has been having recurrent severe ENL beginning 4 years prior to his MDT treatment. Uncontrolled ENL can lead to secondary amyloidosis.

In cases of difficult to treat ENL, some drugs reported as useful have been azathioprine [J Clin Diag Res 2017;11:FD01] minocycline [JAMA Dermatol 2015;151:1026], and etanercept [Ann Bras Dermatol 2017;92:575 and Clin Infect Dis 2011;52:e133].

We would like to thank Pedro Legua MD, Universidad Cayetano Heredia, for providing insightful case discussion.