小龍醫師館

內科-惠氏病,臨床醫學教室

惠氏病一種革蘭陽性放線菌感染引起的全身性疾病。疾病特徵是腹瀉、體重減輕、關節炎；小腸粘膜活檢具有特異性和診斷價值。基因檢測法可用於不典型的Whipple disease患者。

惠氏病(Whipple disease，WD)一種罕見的、由細菌感染引起的全身性疾病(Whipples disease is a rare bacterial infection that may involve any organ system in the body)，但主要影響是小腸，多見於白人40歲以上男子。近年來，將細菌的16S rRNA gene在分子水準擴增分析，依據其分子演化的結果，將Whipple病改名為Tropheryma whippelii(Phylogenetic analysis of these sequences revealed a new bacterial species related to the actinomycete branch which was named “Tropheryma whippelli”)，證實是一種革蘭陽性桿菌----放線菌(actinomycete)感染所致，此病菌常存在廢水中。疾病特徵是腹瀉、腹痛及嚴重的吸收不良、體重減輕(The gastrointestinal tract is the most frequently involved organ, with manifestations such as abdominal pain, malabsorption syndrome with diarrhea, and weight loss)、多發性關節痛和關節炎(90%)、咳嗽、貧血、色素沉著、肺門淋巴結腫大、胸腔積液。小腸粘膜活檢具有特異性和診斷價值。

最常見的症狀有腹瀉、腹痛、體重減輕(The leading symptoms of Whipples disease are weight loss, diarrhea, and arthropathy)；90%患者可出現急性關節炎，持續數天，大多在膝關節、踝關節、手指關節、髖關節、肩關節、肘關節、腕關節等處，少見永久性損害；有時腸胃道表現不明顯時，應當注意是否有低熱(54%)、淋巴節病變(54%)、色素沉著(40~60%)、心肌炎、胸膜炎、葡萄膜炎、脊柱椎間盤炎、貧血(Other signs include low-grade fever, lymphadenopathy, skin hyperpigmentation, endocarditis, pleuritis, uveitis, spondylodiscitis, and neurological manifestations)；20~30%患者可出現出現中樞神經症狀，造成意識改變、頭痛、複視、視乳頭水腫；20%患者可出現Oculomasticatory myorhythmia 及oculo-facial-skeletal myorhythmia，常伴有supranuclear vertical gaze palsy。由於表現多樣性，增加診斷的困難性，許多病患往往是數年或數十年後才被診斷出來(Due to the wide variability of manifestations, clinical diagnosis is very difficult and is often made only years or even decades after the initial symptoms have appeared)。

1. 淋巴結或小腸粘膜活檢時可見含有糖蛋白的泡沫狀巨噬細胞(foamy macrophages)，其PAS染色陽性，及腸絨毛擴張現象。電子顯微鏡下可見PAS陽性物質是杆狀細菌所構成，其具有三層細胞壁超微結構(It is usually based on the demonstration of periodic acid-Schiff-positive particles in infected tissues and/or the presence of bacteria with an unusual trilaminar cell wall ultrastructure by electron microscopy)。
2. PCR：檢體中若有細菌的16S ribosomal DNA (rDNA) sequence可作為診斷依據。此方法優於組織學檢查。
3. 關節X-ray：少見侵蝕破壞，但偶有骶髂關節炎(sacroiliitis)表現。
4. 腹部CT：可見Lymphadenopathy。
5. HLA-B27：若有中樞骨骼關節炎，8~30%可陽性結果。
6. 其他實驗室檢查：Anemia (75%)、血清Carotene降低(95%)、血清Albumin降低(93%)

許多抗生素都有療效，如penicillin combined with streptomycin、erythromycin、ampicillin、chloramphenicol、 tetracycline、Trimethoprim-sulfamethoxazole(TMP-SMZ)。專家建議，penicillin或ceftriaxone 和streptomycin 連用2個星期後，臨床症狀能很快改善，但因組織學的恢復可能需要2年，故需再服用TMP-SMZ(因可穿過BBB)至少1年(an initial parenteral therapy with penicillin and streptomycin for 2 weeks followed by TMP-SMZ. The regression of histopathological findings is slower. This is probably due to degradation of the bacterial DNA prior to resolution of the rigid bacterial cell wall of)以預防中樞神經症狀復發。然而，中樞神經症狀的復發提示較差的癒後及較高的死亡率(CNS relapses have a poor prognosis and are associated with a high mortality rate)，有必要時需做腦脊隨液檢查。一般複查PCR，若呈陰性結果表示抗生素治療有效(positive PCR results may become negative, suggesting an efficacy of the antibiotic treatment)。

惠氏病、腹瀉、體重減輕、關節炎、小腸粘膜、革蘭陽性桿菌、放線菌Whipple disease