Lucio Phenomenon in an Adolescent Female

Leprosy is a neglected tropical disease that, despite considerable efforts, remains a major healthcare burden in many underdeveloped and developing countries.¹ In the year of 2017, 80.2% of the new cases reported globally were located in 3 countries: India, Brazil, and Indonesia. In the Americas region, Brazil is the country with the highest burden, accounting for 92.3% of new leprosy cases.² Between 2014 and 2018, the average incidence rate in Brazil was 13.64 new cases per 100000 inhabitants.³

Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae that primarily affects the skin and peripheral nerves. Contrary to popular belief, leprosy is not highly contagious, and treatment is readily available.^1,3 Through awareness and early medical intervention, significant reduction in disability related to the eyes, hands, and feet is possible. Relapses tend to be rare; however, any damage caused by neuropathy is irreversible and may require lifelong care.³ Kamath et al stated that: “immunologic reactions are an important aspect of leprosy that markedly affect the disease course and associated disability. The reactions may occur before, during, or after treatment with MDT. Reversal reaction (type 1), erythema nodosum leprosum (type 2), and LP are the 3 leprosy reactions, and they most commonly occur in patients with the lepromatous and borderline categories of the disease.”⁴ Although Brazil has the world’s second highest incidence of leprosy,^1,2 few cases of LP are reported in the Brazilian literature.⁵

The case of an adolescent treated for LP is presented herein. Written informed consent for publication of this report and accompanying images was obtained from the patient’s parents.

A 17-year-old female from Nova Iguaçu, Rio de Janeiro, Brazil, presented to an outside general hospital emergency department with “extensive body wounds.” The patient was admitted and underwent treatment with IV antibiotic therapy (ceftriaxone and clindamycin) for 7 days, with no improvement of the lesions. Other symptoms persisted as well, including fever (temperature of up to 38.7 °C), tachycardia, and adynamia. The patient was then transferred to the authors’ hospital, a tertiary reference center for infectious diseases, for specialized care.

Past medical history included a diagnosis of borderline lepromatous leprosy that was treated with an MB-MDT scheme with rifampicin (600 mg/month), dapsone (100 mg/day), and clofazimine (50mg/day and 300 mg/month). Anemia occurred in the second month after MB-MDT was started, and dapsone was replaced with ofloxacin 400 mg/day (alternative MB-MDT) to complete the 12-month course of treatment. The patient also had suffered a first trimester spontaneous abortion 2 months before the current clinical presentation.

On clinical and dermatologic examination, she was in distress; dehydrated and tachycardic; and had several hyperchromic and purplish macular lesions, erythematous plaques, multiple blisters with serohematic content, and necrotic ulcers on the lower and upper limbs, ears, nose, palms, and soles (Figure 1). There were signs of arthritis in her wrist and index finger of her left hand. She also had bilateral but slightly asymmetrical amyotrophic fingers (Figure 1), pain and thickening on palpation of the ulnar nerves, and paresthesia in boot-glove pattern.

Laboratory examination results included hypochromic microcytic anemia (hemoglobin level, 7.2 g/dL) with anisocytosis; reticulocyte count of 1.42% (reticulocyte production index, 0.36); platelet count, 624000/uL; and white blood cell count, 28040/uL. The leukocyte differential count was myelocytes 3%, metamyelocyte 5%, band neutrophil 17%, segmented neutrophil 59%, lymphocytes 12%, and monocytes 4%; with high levels of C-reactive protein (28.67 mg/L), ferritin (2247 ng/mL), and canalicular enzymes (γ-glutamyltransferase, 367 U/L; alkaline phosphatase, 158 U/L). Her serology tests were negative for hepatitis B, hepatitis C, HIV, and syphilis. Blood cultures for bacteria and fungi and a β-human chorionic gonadotrophin urine test were also negative. 

Skin smear microscopy detected acid-fast bacilli and globi in all samples (earlobe: right [1+], left [4+]; elbow: right [3+], left [2+]; bacterial index, 2.5+), which were also observed in the microscopic evaluation of liquid content of the blisters (Figure 2A).

A skin biopsy was performed; histopathologic examination revealed superficial and deep inflammatory perivascular and periadnexal granulomatous dermatitis and the presence of neutrophils, leukocytoclasia, and vascular fibrinoid deposits in the interstice. Although no thrombus was visualized, the other findings suggest thrombogenic activity. Wade staining showed numerous, largely fragmented
bacilli, which is compatible with reactional or treated MB leprosy (Figure 2B-2E).

Based on the clinical, histopathologic, and skin smear features, a diagnosis of borderline lepromatous leprosy in reactional state (ie, LP) was made.

Ivermectin (200 mcg/kg) was prescribed for 2 consecutive days (prophylaxis for strongyloidiasis), followed by IV pulse therapy of methylprednisolone (1000 mg) for 3 consecutive days; improvement in fever, tachycardia, and arthritis and reduction of hyperchromia and macular area were noted. Alternative MB-MDT with rifampicin (600 mg/month), ofloxacin (400 mg/day), and clofazimine (50mg/day and 300 mg/month) was restarted in association with prednisone 50 mg per day and pentoxifylline 1200 mg per day.

The patient was discharged from the hospital. Twenty-one days after hospital discharge, the patient underwent surgical debridement of the necrotic lesions (Figure 3A and 3B). As of this writing, the patient is still being followed up monthly as an outpatient at a referral center, maintaining adherence to the prescribed treatment and daily local therapy in which sterile normal saline (0.9% sodium chloride) is used for cleansing, followed by dressing with silver sulfadiazine ointment. Some lesions had fully healed, and others were in the final stages of healing (Figure 3C) at the 2-month follow-up visit.

LP, or erythema necrotisans, is an uncommon reaction characterized by severe necrotizing cutaneous lesions that occurs in patients with Lucio’s leprosy and lepromatous leprosy.^6,7 Although most reported cases of LP occurred in Mexico, cases have been described in several other countries as well.^8-11 LP is an acute, rare condition that is characterized initially by outbreaks of erythematous macules with slight infiltration; over time, it progresses to include central necrosis and subsequent ulceration.¹² Latapi and Zamora¹² were the first to note the presence of flaccid and dark blisters, which, after rupturing, could leave a deep ulceration, usually preceded by pain. Lesions preferentially affect the extremities, leaving atrophic and stellar scars.¹²

Some authors consider the prognosis of LP to be severe, being potentially life threatening due to dyscrasia or sepsis. Triggering factors for LP are intercurrent infections,¹³ drugs,¹⁴ respiratory infections, and even pregnancy.^7,15 In a study published in 1952 involving 52 pregnancies in 26 women with a diagnosis of active lepromatous leprosy, King and Marks¹⁶ observed a worsening of leprosy in 78% of pregnant women who did not receive sulfone drugs compared with worsening in 22% of pregnant women who did receive sulfone drugs. It is possible that pregnancy was a trigger for the leprosy reaction as described in this report.

The 3 criteria used to define LP are cutaneous ulceration, vascular thrombosis, and invasion of the blood vessel walls by Hansen bacillus.^6,11 Historically, it has been difficult to classify LP. In 1998, Rapini¹⁷ suggested that LP be classified as type 3 reaction, with an anatomopathological substrate of lepromatous leprosy and leukocytoclastic vasculitis with a strong tendency to thrombosis, necrosis, and ulceration, in addition to massive invasion of the endothelium by mycobacteria. According to Frade et al,⁵ LP’s histopathological features are: endothelial proliferation, thrombosis, ischemic necrosis, and a discrete mononuclear infiltrate along with the infiltrate of lepromatous leprosy. Reaand Jerskey¹⁸ reviewed histologic material obtained from LP lesions and endothelial proliferation did not occur in all cases.

Similarly to the case reported by Faye et al¹⁹, this patient lacked histological evidence of thrombosis and endothelial cell invasion by M leprae that characterize LP. However, her clinical features, with multiple spontaneous skin ulcerations and numerous acid-fast bacilli in skin slit smear test, met the diagnostic criteria for LP. These symptoms could not be attributed to any disease other than leprosy. The inefficacy of antibiotics also ruled out the possibility of common bacterial infection initially suspected.

Because of the small number of LP cases studied and reported in the international literature, there is no consensus regarding the best treatment for this reaction.⁵ Most reports suggest that MDT or alternative-MDT and systemic steroids²⁰ should be used in the management of LP. It is also important to be aware of the risk of concurrent sepsis and to treat it immediately, should it occur. Some authors believe that LP should be treated with systemic corticosteroids and thalidomide.⁶ However, there is no consensus in the literature regarding whether or not to use thalidomide in patients without previous erythema nodosum leprosum.⁶ Thalidomide remains contraindicated in pregnant women, women of childbearing age, and sexually active men who are not using contraception.

Herath et al⁹ followed a patient with LP secondary to lepromatous leprosy who also developed anemia. According to guidelines on the management of MB leprosy, due to the adverse event of anemia, dapsone should be replaced and the patient was instructed to use daily doses of clofazimine and ofloxacin and monthly doses of rifampicin and clofazimine under supervision, along with frequent cleaning and dressing of ulcerated areas. Araujo Dantas et al²¹ reported that alternative-MDT is effective even in patients with advanced disease with tendon exposure.

Based on the lack of treatment consensus data, the authors of this case report restarted the alternative MB-MDT treatment combined with systemic corticosteroid and pentoxifylline, which has been reported to improve blood flow and prevent platelet aggregation.¹⁹

Cutaneous ulceration is always present in LP⁶ and wound assessment is crucial to determine the appropriate treatment plan.²² The primary goal of debridement is to remove all the devitalized tissue from the wound bed to promote wound healing. It reduces the malodour associated with the bacterial burden within the wound, controls ongoing inflammation by removing the necrotic tissue and biofilm, and encourages the formation of granulation tissue.^22,23 Historically, several types of wound debridement techniques have been described in clinical practice, such as: autolytic; enzymatic; biodebridement (eg, larval therapy [ie, maggot debridement therapy], which involves the use of sterile larvae of the green bottle fly Lucilia sericata to remove the dead tissue); mechanical; conservative sharp; and surgical.^22,24

For wounds with adherent slough or dry black necrotic tissue, as in this case report, surgical debridement may be necessary.²² According to Gray et al,²⁵ conservative sharp and surgical debridement comprise the current standard of care against which other forms of therapy are measured. These techniques are quick and effective, but they must be performed by a competent practitioner with specialist training and can be expensive. Surgical debridement is particularly expensive, with the associated need for operating room time and hospital admission.

Based on reports of similar cases,^26,27 the patient in this case report was treated with surgical debridement of necrotic lesions, and daily local therapy was maintained with sterile normal saline (0.9% sodium chloride) as the wound cleansing solution followed by dressing with silver sulfadiazine ointment. The patient has shown good response to this treatment.

Atypical cutaneous ulcers are caused by inflammatory, neoplastic, vasculopathic, hematologic, infectious, and drug-induced etiologies and require a complex therapeutic approach.²⁸ Wound cleansing helps optimize the healing environment and decreases the potential for infection.²⁸ Topical antimicrobial dressings, including those that contain silver, iodine, or polyhexamethylene biguanide and bacterial binding dressings are used locally to control or manage infection.²⁸ As Janowska et al²⁸ reported, “compression bandaging increases healing in inflammatory ulcers, vasculopathies and heroin ulcers and controls the underlying vascular damage.” Unfortunately, the authors of this case report did not have access to these therapeutic modalities.

The limitations of the current article include its design as a single case. In addition, there are limited published cases of LP available, and this report only describes the authors’ personal experience.

LP is a rare and potentially fatal manifestation of leprosy and that has a high bacterial index. Hormonal alterations cause immunological imbalance, and pregnancy can be associated with exacerbation of symptoms. There is no consensus about the treatment of LP and debridement is required to excise nonviable tissue and promote wound healing. Although this case occurred in a country with a higher burden of leprosy, the current report should increase awareness of this neglected tropical disease and raise suspicion for nonautochthonous, new cases of leprosy in non-endemic areas.