Is it Lucio Phenomenon or Necrotic Erythema Nodosum Leprosum?

Lucio phenomenon (LP) or erythema necroticans is a relatively rare, peculiar reaction pattern occurring in untreated lepromatous (LL) or borderline lepromatous (BL) leprosy cases. A 38-year-old male, a cook by occupation, was referred to the dermatology clinic from otolaryngology department with blistering over both the hands and feet of 2 days duration. He had been admitted 1 week back with epistaxis and nasopharyngeal myiasis in otolaryngology department. He was started on systemic antibiotics gentamycin, crystalline penicillin, and metronidazole with nasal instillation of turpentine oil 2 drops 6 times a day. Two days later, he had developed edema with painless hemorrhagic blistering over the dorsum of left hand followed by involvement of the right hand, dorsa of both feet, and both the earlobes within a day. Histopathology of the blister showed sub-epidermal blister, with necrotizing leukocytoclastic vasculitis of papillary dermal vessels with thrombosis, numerous acid-fast bacilli in macrophages, and macrophage granulomas extending up to subcutis. In view of the absent fever or constitutional symptoms, and the classical angular infarcts and hemorrhagic blisters evolving into ulcers with angulated margins, we considered LP as the most likely diagnosis. The patient was started on a combination of WHO recommended multibacillary anti-leprosy therapy and prednisolone (40 mg/day).

What was known?

Vasculonecrotic reactions presenting as bullae and ulcers usually occur in BL and LL patients, either as Lucio's phenomenon or erythema nodosum (EN) with necrosis. Lucio's phenomenon usually appears in untreated or inadequately treated non.-nodular lepromatous leprosy.

Introduction

Lucio phenomenon (LP) or erythema necroticans was first described by Lucio and Alvarado and later confirmed by Latapi and Zamoraas a vasculitis occurring in diffuse non-nodular form of leprosy, which they called as “pure and primitive.” It is a relatively rare, peculiar reaction pattern occurring in untreated lepromatous (LL) or borderline lepromatous (BL) leprosy cases. LP is endemic in Mexico although cases have been reported from USA, Spain, South and Central America, including Brazil,[1] and Asia.[2] We herewith present a case of LP in a 38-year-old male.

Case Report

A 38-year-old male, a cook by occupation, was referred to the dermatology clinic from otolaryngology department with blistering over both the hands and feet of 2 days duration. He had been admitted 1 week back with epistaxis and nasopharyngeal myiasis in otolaryngology department. He was started on systemic antibiotics gentamycin, crystalline penicillin, and metronidazole with nasal instillation of turpentine oil 2 drops 6 times a day. Two days later, he had developed edema with painless hemorrhagic blistering over the dorsum of left hand followed by involvement of the right hand, dorsa of both feet, and boththe earlobes within a day, thus was referred to us.

There was no history of fever, arthralgia or any other constitutional symptoms in the past 2 days. He gave history of recurrent blistering of hands and feet for the past 1 year. On cutaneous examination, multiple hemorrhagic bullae measuring 1-2 cms were seen over the dorsum of both hands and fingers feet and toes [Figure 1a], with surrounding purpuric macules. Similar vesicles and erosions covered with hemorrhagic crust were present over the helices of both the ears [Figure 1b]. Scattered angular purpuric macules were present over the extensor aspect of the arms and above the ankles. Within 2 days, these bullae had ruptured leaving large deep irregular ulcers with angulated margins.

Figure 1

(a) Hemorrhagic blisters and purpuric macules over dorsum of both the feet (b) Clear fluid filled vesicles and hemorrhagic crusting present along the rim of the right ear

Besides this, there was diffuse infiltration of the face with saddle nose deformity. Skin over the back was diffusely infiltrated with a shiny appearance and intact sensation. The peripheral nerves were symmetrically thickened and non-tender. Bilateral glove and stocking anesthesia was present. Mobile ulnar claw deformity of both the hands was noted. He had resorption of the right little finger, pseudo-ainhum of the right fourth toe, and an amputated left second toe. Examination of the cranial nerves was normal in him.

Slit skin smear from the earlobes revealed the presence of globi. The average bacteriological index was 4 +. With the above findings, a provisional diagnosis of diffuse non-nodular form of lepromatous leprosy with grade 2 deformity of hands and feet was made. A differential diagnosis of LP, drug-induced pseudoporphyria, drug-induced vasculitis, cryoglobulinemic vasculitis, and necrotic erythema nodosum leprosum were considered for the hemorrhagic bullae, ulcers, and purpuric macules.

Hemogram was normal, except for neutrophilic leukocytosis. Erythrocyte sedimentation rate was 56 mm in the first hour. Liver, renal function tests and urine examination were normal. VDRL (Venereal disease research laboratory test) for syphilis, ELISA for human immunodeficiency virus (HIV), and hepatitis B surface antigen were negative. Urine examination for porphyrins was negative. Serum cryoglobulins, rheumatoid factor (RF), and anti-nuclear antibody (ANA) were negative. Skiagram of both the hands and feet did not show any evidence of osteitis or osteomyelitis.

Biopsy from the infiltrated skin over the back showed atrophic epidermis, free Grenz zone, diffuse and periadnexal macrophage granulomas with strong Fites' stain positivity for M. leprae consistent with lepromatous leprosy [Figure 2a]. Histopathology of the blister showed sub-epidermal blister, with necrotizing leukocytoclastic vasculitis of papillary dermal vessels with thrombosis [Figure 2b], numerous acid-fast bacilli in macrophages, and macrophage granulomas extending up to subcutis. We were not able to demonstrate the acid-fast bacilli within the endothelial cells.

Figure 2

(a) Atrophic epidermis, thin Grenz zone and diffuse macrophage granulomas in the upper dermis (H and E, stain at ×40 magnification). (b) Papillary dermal vessels showing evidence of leukocytoclastic vasculitis (H, and E stain at ×40 magnification)

In view of the absent fever or constitutional symptoms, and the classical angular infarcts and hemorrhagic blisters evolving into ulcers with angulated margins, we considered LP as the most likely diagnosis. The patient was started on a combination of WHO recommended multibacillary anti-leprosy therapy and prednisolone (40 mg/day). There were no new lesions after start of therapy. Prednisolone was tapered after 1 month by 5 mg every 2 weeks and subsequently stopped. The ulcers healed slowly with depigmented scars after 10 weeks [Figure 3].

Figure 3

Healing ulcers two and a half months after starting therapy

Discussion

Vasculonecrotic reactions presenting as bullae and ulcers usually occur in BL and LL patients, either as LP or erythema nodosum (EN) with necrosis.[3]

LP usually appears in untreated or inadequately treated non-nodular lepromatous leprosy[4] patients after a median of 1 to 3 years after the first manifestations of the disease and presents with erythematous mildly-painful areas over the extremities, which evolve into necrotic, geometric-shaped or jagged-edged ulcers of 0.5 to 1 cm in size.[45] There is usually no associated fever, constitutional symptoms, visceral involvement or neuritis. When the inflammation is severe, a hemorrhagic blister is formed, which breaks down to leave a deep ulcer with jagged edges surrounded by an inflammatory zone[6] as seen in our case. These ulcers usually heal in 2 weeks to form atrophic scars in the classical description given by Latapi and Zamora. Rea et al.[7] have reported ulcers sized 10 cms and an average healing time of 4 months in a retrospective study of 30 patients with LP.

Vasculonecrotic erythema nodosum usually occurs in multibacillary LL and BL cases after starting multidrug therapy. The patients develop severe, deep painful ulcers associated with constitutional symptoms, visceral involvement, and neuritis.[8] The ulcers heal with fibrotic scars.[3] Even though there have been various reports in the past of EN with necrosis occurringin untreated cases of multibacillary leprosy,[9-11] they were allassociated with fever and constitutional symptoms, which was conspicuously absent in our case.

Our patient had a diffuse non-nodular form of lepromatous leprosy with glove and stocking anesthesia and saddle nose. He had never been treated for Hansen's disease in the past. He presented with necrotic angular infarcts without any constitutional symptoms, which evolved into deep ulcers with angulated margins. Clinical features in our patient were consistent with LP although complete histological picture was not present.

There is no consensus on the histopathological abnormalities in LP. Histopathologically, Lucio's phenomenon has been reported to have 2 types of patterns. One of them involves leukocytoclastic vasculitis as the underlying pathologic change, and the other, endothelial cell proliferation, thrombosis, a mild mononuclear cell infiltrate and ischemic necrosis.[12] Some common histopathological findings seen in different case reports of LP in the past are tabulated and compared below [Table 1].

Table 1

Comparison of histopathological features found in various reports of Lucio phenomenon in the literature

The differing histological descriptions could be due to the site and timing of the biopsy as the histopathological features vary as LP evolves.[4] The absence of AFB in endothelial cells in our case could be explained by the extensive destruction of vessel walls by necrotizing vasculitis. The classical clinical picture of LP in our case supported the diagnosis of LP.

Conclusion

LP is very rarely reported from India despite the huge load of multibacillary cases. This could be due to lack of clinical suspicion or due to inconsistent features on histopathology. We report this case to highlight the difficulties in differentiating LP from necrotic erythema nodosum in diffuse non-nodular lepromatous leprosy cases. [16]

What is new?

Presence of fever and constitutional symptoms help to separate eythema nodosum necroticans from Lucio's phenomenon.