The Lucio's phenomenon (necrotizing erythema) in pregnancy

Abstracts

O fenômeno de Lúcio, variante do estado reacional hansênico tipo 2, provavelmente mediado por imunocomplexos, caracteriza-se por reação cutânea necrosante grave que ocorre principalmente em doentes portadores de hanseníase virchowiana não nodular. Os autores relatam o caso de uma paciente de 27 anos, do sexo feminino, gestante de 32 semanas, com quadro de lesões eritêmato-purpúricas nos membros, bem delimitadas, confluentes, encimadas por bolhas, algumas necróticas e ulceradas, com uma semana de evolução, acompanhadas de febre e intensa dor local. A baciloscopia da linfa evidenciou bacilos álcool-acidorresistentes formando globias, e a histopatologia da pele confirmou hanseníase virchowiana, compatível com fenômeno de Lúcio. Foi iniciada prednisona e poliquimioterapia multibacilar com rifampicina, clofazimina e sulfona, com boa evolução. A gravidez tem sido associada à elevada incidência de aparecimento dos primeiros sinais ou ao agravamento da hanseníase por alterações hormonais que levam ao desequilíbrio imunológico, sendo considerado crítico o período compreendido entre o último trimestre de gestação e os primeiros três meses da lactação, quando a imunossupressão atinge seu ápice. Apesar da recomendação de se restringir a ingestão de drogas na gestação, o tratamento da hanseníase deve ser realizado, visto que seus benefícios superam os riscos.

eritema; gravidez; hanseníase

CASE REPORT

The Lucio's phenomenon (necrotizing erythema) in pregnancy^*

Karin Adriane Helmer^I; Isabela Fleischfresser^II; Luciana D. Kucharski-Esmanhoto^III; José Fillus Neto^IV; Jesus Rodriguez Santamaria^V

^IM.D. Dermatologist

^IIResident M.D., 3^rd year of Dermatology

^IIIM.D. Dermatologist

^IVAdjunct professor of Pathology - Federal University of Parana

^VAssistant professor of Dermatology - Federal University of Parana

^{Correspondence}

SUMMARY

The Lucio's phenomenon, a type 2 reactional condition in leprosy probably mediated by immune complexes, is a severe necrotizing skin reaction that occurs mainly in patients with non-nodular lepromatous leprosy. This report presents a 27-year-old woman, in her 32nd week of pregnancy, with a one-week history of painful skin lesions in extremities, reddish-purple, sharply delineated, confluent, with bullae and occasional necrosis and ulceration. The patient also referred fever. Baciloscopy showed acid-fast bacilli and globi, and the histopathologic findings of a skin biopsy were consistent with lepromatous leprosy and Lucio's phenomenon. Prednisone and multidrug therapy with rifampin, clofazimine and dapsone were given, with remission. Pregnancy has been associated with a high incidence of first diagnosis of leprosy or with an exacerbation of symptoms in patients with the established disease because hormonal alterations cause immunological imbalance, particularly between the last three months of pregnancy and the first three months of lactation, when immunosuppression is higher. Despite the recommendation not to take drugs during pregnancy, the multidrug therapy regimen must be used, since the benefits achieved with the treatment surpass the risks.

Keywords: erythema; pregnancy; leprosy.

INTRODUCTION

Leprosy is a chronic infectious disease caused by the acid-fast bacillus Mycobacterium leprae, transmitted by inhalation following exposure of a person with an untreated bacilliform infection, usually during intimate and prolonged contact. Depending on the patient's immunity, the infection may develop toward recovery or the clinical forms of the disease: indeterminate, tuberculoid, dimorphic or lepromatous, each of which may course with episodes of acute inflammation called "reaction or reactional states". Type 1 reactions are mediated by cellular immunity and clinically present neuritis or a reverse reaction. Those of type 2 involve the immunocomplex and cytokine production, such as tumoral necrosis factor alpha,¹ and include erythema nodosum leprosum, multiform erythema, Lucio's leprosy phenomenon and neuritis.²

Lucio's leprosy phenomenon was described by Lucio and Alvarado in 1852 in Mexico, and was so named in 1948 by Latapi and Zamora.³ It represents a variant of lepromatous reaction type 2 and histopathologically is characterized by acute necrotic vasculitis, being synonymous with the expression "necrotizing erythema".² This can occur in Lucio's leprosy (where it forms a pure and primitive lepromatosis) and in other forms of lepromatous leprosy.^4,5

The exacerbation of leprosy at the end of gestation and in the puerperium was described for the first time by Ryrie, in 1938, who declared: "Leprosy does not present any effects on the course of the pregnancy, however, the pregnancy exercises an important effect on the course of the leprosy".⁶ Since then, gestation has been associated with the high incidence of onset of the first signs or aggravation of leprosy.

This work presents the case of a 27-year-old pregnant woman, in the thirty-second week of gestation, with ulcerous necrotic lesions in the extremities, diagnosed as diffused non-nodular leprosy with vasculitis of Lucio's leprosy phenomenon.

CASE REPORT

The authors herein present a 27 year old female patient, 32 weeks pregnant, who had reported a burn with scalding water on the left leg seven months previously, resulting in a lesion of difficult cicatrization. Two weeks earlier, a secondary infection had presented itself in that area, there had been no improvement despite having used cefazolin, heparin and symptomatic medication. It developed with the appearance of purpuric lesions in the inferior and superior members and in the abdomen, accompanied by pain and fever.

Regarding personal history, this was her second gestation and she did not refer any problems during the first. She denied smoking, alcoholism or drug addiction. When questioned about family antecedents, she affirmed that she was not aware of similar occurrences.

At admission she was in a regular general state, with stable vital signs and afebrile. A dermatological exam showed infiltrated facies with telangiectasia and madarosis (Figure 1), edema and extensive erythema in the members, with disseminated and confluent erythematous-purpuric lesions, topped by blisters with well-defined borders, some with ulcerated and necrotic areas (Figures 2 and 3) and bilateral inguinal enlarged lymph nodes.

Laboratory exams showed hypochromic microcytic anemia, leukocytosis with deviation to the left, increase in the erythrocyte sedimentation rate, anti-HIV, VDRL and non-reagent anticardiolipin antibodies.

Bacilloscopy of the lymph revealed acid-fast bacilli with the formation of globi, bacilloscobic index = 1, with 5% complete bacilli, and 95% granular bacilli. Examination of the biopsy of apparently healthy skin but with lesions using hematoxylin and eosin stain showed leukocytoclastic vasculitis with fibrinoid necrosis (Figure 4), foamy histiocytes occupying the lobular portion of the hypodermis (Figure 5) and presence of numerous granular bacilli determined by Fite-Faraco (Figure 6). This pattern is compatible with Virchow's leprosy and Lucio's leprosy phenomenon.

Multibacillary polychemotherapy was initiated with rifampicin 600mg/month, clofazimine 300mg/month and 50mg/day and dapsone 100mg/day administered with prednisone 60mg/day, which was reduced progressively over an eight-week period, with good clinical results (Figure 7).

The gestation developed to term for a normal childbirth, without concurrent disease. The newborn was of appropriate weight for gestational age and without malformations.

DISCUSSION

Lucio's leprosy phenomenon represents a serious cutaneous necrotizing reaction that can occur in Lucio's leprosy and also in other forms of lepromatous leprosy.^4,5

Lucio's leprosy is most common in Mexico and Central America and little found in other ethnic groups,^2,7 it is characterized by diffuse infiltration of the skin, madarosis and loss of eyelashes, giving "a swollen, edematous look" to the skin.⁴ Generally, three to four years after onset of the disease³ and usually in untreated patients,⁷ Lucio's leprosy phenomenon establishes itself with the emergence of painful erythematous discoloration that courses into necrosis and ulceration.^3,8 This development is ascendant (inferior members, superiors, buttocks, trunk and, with lesser frequency, the face)⁹ and resolves in a period that varies from two to four weeks, leaving atrophic scars.

In other forms of lepromatous leprosy, Lucio's leprosy phenomenon is characterized by necrosis in lesions of nodular or polymorphic erythema that appear in the course of a lepromatous reaction in patients with nodular or non-nodular lepromatous leprosy.^4,5 Although Brazil occupies second place in the world according to the number of cases of leprosy, reports of Lucio's leprosy phenomenon are rare.¹⁰

Laboratory findings always present anemia, leukocytosis and deviation to the left. Examination of the lymph generally presents a high bacilloscobic index^4,8 (not found in the described case, probably due to a technical flaw while performing the tests). In the histology, infiltrated inflammation with foamy histiocytes are observed together with vascular damage due to direct invasion by M. leprae into endothelial cells⁷ causing vasculitis and thrombosis of the superficial and deeper vessels with consequent hemorrhage and infarction of the skin. Acid-fast bacilli can be detected with Ziehl or Fite-Faraco stains.^3,4,10 These findings are observed as much in the clinically altered skin as in the apparently healthy skin.²

Treatment consists of polychemotherapy for multibacilli and sometimes systemic corticoids for control of the reactions. Unlike erythematous nodular leprosy, Lucio's leprosy phenomenon when it occurs in Lucio's leprosy does not present a good response to thalidomide.^9,11

Pregnancy has been associated with a high incidence of onset of the first signs or aggravation of leprosy. The critical period is considered to be between the last quarter of gestation and the first three months of nursing due to hormonal, metabolic and immune system alterations. In gestation cellular immunity is relatively suppressed, mainly in the third quarter, leading to the unchaining or worsening of type 2 reactions, as in the described case. There is also the risk of recurrence of the disease.¹² In the puerperium there is a relative suppression of the humoral immunity, with a greater risk for the development of type 1 reactions beginning between the third and sixteenth week of postpartum.⁶

Newborn whose mothers presented leprosy during pregnancy tend to weigh less than the mean for the general population¹² and present a higher incidence of respiratory problems,¹³ due to placental inadequacy and consequent intra-uterine growth retardation. Nevertheless there is no conclusive controlled study that provides evidence of complications in a gestation as a result of having been treated with polychemotherapy.⁶ Although the newborn may present intercurrent disease, such as foleate dermatitis in the first hours of life due to the sulfone and impregnation of clofazimine in the skin, which presents a brownish coloration.¹²

Women should be encouraged to treat leprosy with polychemotherapy before considering a future pregnancy.¹³ In a recent publication, the Ministry of Health (Ordinance 1073-26 Sept. 2000),¹⁴ recommended the treatment of pregnant women with leprostatics (rifampicin, clofazimine and dapsone) in the standard regimen, despite the usual recommendation of restricting the ingestion of drugs in the first quarter of pregnancy. It was considered that the benefits of the treatment outweigh the risks.

The clinical picture, laboratory exams and histopathology in the described case confirm the diagnosis of non-nodular lepromatous leprosy with Lucio's leprosy phenomenon. The gestation being associated with the diagnosis of infection and to the virulent reactional state type 2, which was probably related to the physiologic immunosuppression of this period. q

REFERENCES

Received in August, 17^th of 2001

Approved by the Consultive Council and accepted for publication in October, 28^th of 2002

• 1. Foss NT. Hanseníase: aspectos clínicos, imunológicos e terapêuticos. An Bras Dermatol 1999 (Mar-Abr); 74(2): 113-119.
• 2. Gilbert E, Cubria JL, Gratacos R, et al Lepra de Lucio. Med Cut ILA 1982; 10: 41-46.
• 3. Pursley TV, Jacobson RR, Apisarnthanarax P. Lucio's Phenomenon. Arch Dermatol 1980(Feb); 116: 201-04.
• 4. Pereira Jr AC. Hanseníase de Lucio. An Bras Dermatol 1993(Jan-Fev); 68(1): 33-40.
• 5. Buffon LP, Leal R, Vidigal MR, Gatti TSR, Pires MC, Reis VMS. Fenômeno de Lucio (eritema necrosante) na gestação: relato de caso e revisão da literatura. An Bras Dermatol 2001 (Jul-Ago); 76(4): 441-448.
• 6. Lockwood DNJ, Sinha HH. Pregnancy and leprosy: A Comprehensive Literature Review. International Journal of Leprosy 1999; 67(1): 06-12.
• 7. Rea TH, Ridley DS. Lucio's Phenomenon: A Comparative Histological Study. International Journal of Leprosy 1979; 47(2): 161-66.
• 8. Saúl A, Novales J. La Lèpre de Lucio-Latapi et le Phénomène de Lucio. Acta leprol 1983 (Jul-Sep);1(3) : 115-32
• 9. Bernadat JP, Faucher JF, Huerre M. Lèpre lépromateuse diffuse révélée par une vasculite cutanée. Ann Dermatol Venereol 1996; 123: 21-23.
• 10. Souza CS, Roselino AMF, Figeiredo F, Foss NT. Lucio's Phenomenon: Clinical and Therapeutic Aspects. Int J Lepr Other Mycobact Dis 2000 Dec; 68(4): 417-425.
• 11. Rea TH, Levan NE. Lucio's Phenomenon and Diffuse Nonnodular Lepromatous Leprosy. Arch Dermatol 1978(Jul); 114: 1023-1028.
• 12. Lopes VGS, Sarno EN. Hanseníase e Gravidez. Rev Ass Med Brasil 1994; 40(3): 195-201.
• 13. Morrison A. A woman with leprosy is in double jeopardy. Lepr Ver 2000; 71(2): 128-143.
• 14. Portaria n º 1073/GM de 26 de setembro de 2000. Publicada no D.O.U. - 100-E - página 18 - Seção 1 de 28 de setembro de 2000.

*

Work done at "Hospital de Clínicas da Universidade Federal do Paraná".

Publication Dates

• Publication in this collection
  09 June 2004
• Date of issue
  Apr 2004

History

• Accepted
  28 Oct 2002
• Received
  17 Aug 2001