Interventions for erythema nodosum leprosum

 

Abstract

Background

Erythema nodosum leprosum (ENL) is a serious immunological complication of leprosy, causing inflammation of skin, nerves, other organs, and general malaise. Many different therapies exist for ENL, but it is unclear if they work or which therapy is optimal.

Objectives

To assess the effects of interventions for erythema nodosum leprosum.

Search methods

We searched the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 1, 2009), MEDLINE (from 2003), EMBASE (from 2005), LILACS and AMED (from inception), CINAHL (from 1981), and databases of ongoing trials, all in March 2009. We checked reference lists of articles and contacted the American Leprosy Missions in Brazil to locate studies.

Selection criteria

Randomised controlled trials (RCTs) of interventions for ENL in people with leprosy.

Data collection and analysis

Two authors performed study selection, assessed trial quality, and extracted data.

Main results

We included 13 studies with a total of 445 participants. The quality of the trials was generally poor and no results could be pooled due to the treatments being so heterogeneous. Treatment with thalidomide showed a significant remission of skin lesions compared to acetylsalicylic acid (aspirin) (RR 2.43; 95% CI 1.28 to 4.59) (1 trial, 92 participants). Clofazimine treatment was superior to prednisolone (more treatment successes; RR 3.67; 95% CI 1.36 to 9.91) (1 trial, 24 participants), and thalidomide (fewer recurrences; RR 0.08; 95% CI 0.01 to 0.56) (1 trial, 72 participants). We did not find any significant benefit for intravenous betamethasone compared to dextrose (1 trial, 10 participants), pentoxifylline compared to thalidomide (1 trial, 44 participants), indomethacin compared to prednisolone, aspirin or chloroquine treatments (2 trials, 80 participants), or levamisole compared to placebo (1 trial, 12 participants). Mild to moderate adverse events were significantly lower in participants taking 100 mg thalidomide compared to 300 mg thalidomide daily (RR 0.46; 95% CI 0.23 to 0.93). Significantly more minor adverse events were reported in participants taking clofazimine compared with prednisolone (RR 1.92; 95% CI 1.10 to 3.35). None of the studies assessed quality of life or economic outcomes.

Authors' conclusions

There is some evidence of benefit for thalidomide and clofazimine, but generally we did not find clear evidence of benefit for interventions in the management of ENL. However, this does not mean they do not work, because the studies were small and poorly reported. Larger studies using clearly defined participants, outcome measures, and internationally recognised scales are urgently required.

 

Plain language summary

Interventions to treat erythema nodosum leprosum, a complication of leprosy

Leprosy remains a public health issue in poorer parts of the world. In 2007 there were approximately 255,000 new cases reported worldwide. Leprosy (or Hansen's disease) is a chronic infectious disease. The skin and peripheral nerves of people with leprosy contain leprosy bacteria. Leprosy can be cured with a combination of antibiotics. The immune system plays an important role in leprosy and determines if and how the disease will develop. The response of the immune system to the antigens of the leprosy bacteria may cause periods of inflammation in the skin and nerves, called reactions. Reactions are the main cause of acute nerve damage and disability in leprosy and occur in about one third of people with leprosy. One type of reaction is erythema nodosum leprosum (ENL), a serious and often chronic complication of leprosy caused by the immune system. People with ENL have red, painful swellings in the skin and often feel ill due to fever and general malaise. There are several treatments for ENL, including the oral drugs prednisolone, thalidomide, and clofazimine. We undertook a systematic review on this topic as it was not clear which treatments were most beneficial.

Our review included 13 randomised controlled trials involving 445 participants. These trials assessed: betamethasone (1 trial), thalidomide (5 trials), pentoxifylline (1 trial), clofazimine (3 trials), indomethacin (2 trials), and levamisole (1 trial). Generally, the quality of the studies was poor and many were too small to identify important clinical differences even if they existed. Three small trials showed benefit for thalidomide and clofazimine treatment in terms of fewer further reactions, more treatment successes, and less relapses of ENL.

Adverse events were reported in most of the trials, but it was often not possible to compare the occurrence of any adverse events between the experimental group and control group. Most adverse events reported were not too serious, and only a few participants could not complete treatment due to serious adverse events or for other reasons.

Whether the interventions improved the quality of life of participants, was not evaluated in any of the trials.

Although we did not find clear benefits in these series of small, poorly-performed studies, this does not mean that these drugs do not work in the treatment of ENL, only that scientific evidence is insufficient. Future studies should be better designed and use clear definitions and outcomes, including long-term outcomes and quality of life measures.

 

摘要

背景

痲風性結節性紅斑的治療

痲風性結節性紅斑 (Erythema nodosum leprosum, ENL) 是罹患痲風病後，因為免疫反應引發的一種嚴重併發症，可能會造成皮膚、神經和其他器官的發炎，也會引起全身性的倦怠。目前有許多治療痲風性結節紅斑的方法，但是這些治療是否真的有效?究竟哪一種治療是最理想的?目前仍舊沒有定論。

目標

評估痲風性結節紅斑治療的效果

搜尋策略

我們在2009年3月搜尋了Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 1, 2009), MEDLINE (自2003年起), EMBASE (自2005年起), LILACS 和 AMED (自創刊起), CINAHL (自1981起), 同時搜尋了前正在進行中各項試驗的資料庫。我們檢視這些文章中所列出的參考文獻，也聯絡了位在巴西的美洲麻風慈善機構 (American Leprosy Missions) 。

選擇標準

在痲風病人身上治療痲風性結節紅斑的隨機對照試驗

資料收集與分析

兩位作者進行研究的篩選、評估試驗的品質，並且選取所要的數據資料。

主要結論

我們囊括了13個研究，共445個受試者。這些研究的品質大多不太理想，因為治療的歧異性大太，這些結果沒有辦法被整併。這些結果包括了: (1) 與acetylsalicytic acid (aspirin) 作比較，thalidomide對於皮膚病變有較顯著的改善 (RR 2.43; 95% CI 1.28 to 4.59) (1個試驗、92個受試者) 。 (2) Clofazimine的治療優於prednisolone，其治療成功率較高 (RR 3.67; 95% CI 1.36 to 9.91) (1個試驗、24個受試者) 。 (3) Clofazimine的治療優於thalidomide，其復發率較低 (RR 0.08; 95% CI 0.01 to 0.56) (1個試驗、72個受試者) 。 (4) 比起dextrose，靜脈注射betamethasone沒有顯著的助益 (1個試驗、10個受試者) 。 (5) 與thalidomide比較，pentoxifylline 沒有更明顯的改善 (1個試驗、44個受試者) 。 (6) 與prednisolone、aspirin 或chloroquine比較，indomethacin 沒有較好的療效 (2個試驗、80個受試者) 。 (7) 與安慰劑作比較， levamisole 沒有較好的助益 (1個試驗、12個受試者) 。 (8) 每天服用thalidomide 100 毫克的患者發生輕到中度不良反應的機率低於每天服用300毫克的病人 (RR 0.46; 95% CI 0.23 to 0.93) 。 (9) 比起 prednisolone，使用clofazimine 的受試者明顯地有較輕微的不良反應。沒有任何一篇研究評估生活品質或是經濟影響。

作者結論

有一些證據顯示thalidomide和 clofazimine有臨床上的助益，但是整體而言，我們沒有發現足夠的證據證實它們對痲風性結節紅斑的治療有幫助。然而，這並不意味著它們沒有作用，因為這些研究的規模都很小，也沒有被適當地發表。我們迫切需要更大型的研究，包括定義明確的受試者、更好的結果評估和國際認可的評分標準。

翻譯人

本摘要由馬偕醫院黃心穎翻譯。

此翻譯計畫由臺灣國家衛生研究院 (National Health Research Institutes, Taiwan) 統籌。

總結

痲瘋病在落後地區仍舊是一個重要的健康議題。在2007年裡，全世界共有255,000個新診斷的病例。痲風病，或叫作漢生病 (Hansen's disease) 是一種慢性的感染性疾病。罹患痲風病的患者，可以在其皮膚或週邊神經中發現痲風桿菌。這個疾病可以藉由抗生素的合併使用達到治癒的效果。免疫反應在痲風病中扮演著重要的角色，它決定了這個疾病是否會發作，一旦發作了會有什麼表現。免疫系統對痲風桿菌抗原的對抗會引起皮膚和神經的發炎期，這個現象稱為反應 (reactions) 。反應 (reactions) 是引起急性神經損害及殘疾的主要原因，發生在三分之ㄧ的痲風病人身上。痲風性結節紅斑 (Erythema nodosum leprosum, ENL) 就是其中一種反應，這是一種在痲風患者中，由免疫系統引發的嚴重且多半是慢性的併發症。得到痲風性結節紅斑的人在皮膚上會出現發紅疼痛的腫脹，也可能會因為發燒或全身倦怠感到不舒服。目前有很多治療痲風性結節紅斑的方法，包括了口服prednisolone、thalidomide和clofazimine。目前沒有明確的證據顯示哪一種治療是最有效的，因此我們針對這個議題著手進行了一個系統性的回顧。我們的回顧性文章囊括了13個隨機對照試驗，共445個受試者。這些試驗包括了: betamethasone (1 個試驗) 、 thalidomide (5 個試驗) 、pentoxifylline (1 個試驗) 、 clofazimine (3 個試驗) 、indomethacin (2 個試驗) 、和 levamisole (1 個試驗) 。整體而言，這些研究的品質大多不太理想，許多研究的試驗群體太小，即使有變化，也沒辦法辨別出重要的臨床改變。其中三個研究顯示thalidomide和 clofazimine 的治療是有助益的，它們可以減少進一步的反應、增加治療的成功，也使得痲風性結節紅斑的復發率降低。絕大多數的試驗都可以發現治療的不良反應，但是不太能夠去比較實驗組以及對照組不良反應發生率的不同。多數被報導的不良反應都不是太嚴重，只有少數的受試者因為嚴重的不良反應或是其他原因無法完成治療。至今沒有任何一個試驗曾評估這些治療是否可以改善受試者的生活品質。雖然在這些小型且設計不良的研究裡，我們沒有辦法歸納出明確的效果，但這並不意味著這些藥物對於痲風性結節紅斑的治療沒有作用，我們只能說這些研究的證據性不足。未來的研究需要被完善地設計，有明確的定義和結果，其中包括了長期的效果和生活品質評估。