常見皮膚病

高敏感性徵候群又稱為DRESS (藥物疹伴嗜伊紅性白血球血症及全身性症狀drug rash with eosinophilia and systemic symptoms)(Arch Dermatol. 1996 Nov;132(11):1315-21)，日本則稱為DIHS(drug-induced hypersentitivity syndrome)。是指一種特殊的嚴重藥物疹，患者會出現廣泛性且持久性丘疹、膿皰或紅疹，往往擴及全身引起紅皮症。患者會伴隨發燒、淋巴結種大及侵犯內臟，如引起肝炎、肺炎、心肌炎、心包膜炎及腎炎，晚期則可出現甲狀腺功能低下。超過9成患者血液中會出現嗜伊紅性白血球增加，4成會有單核球增加現象，另外也會有血中丙種免疫球蛋白下降。高敏感性徵候群的死亡率可高達10%，皮膚病灶及肝炎現象可持續數週到數月。在台大醫院60位患者的統計中，有5位產生急性腎衰竭(8%)，且其中一位因此而死亡，另一位則需長期洗腎。至於肝臟功能異常雖然高達 80%，但只有4位產生肝衰竭。另有一位在藥物疹一個月後產生甲狀腺亢進症狀，之後發展成 Graves disease。有6位因病發發菌血症(包括細菌及黴菌)而住院，其中三位因此死亡。^{免疫性疾病如糖尿病、紅斑性狼瘡、甲狀腺病、硬皮樣GVHD樣皮疹，也是可能併發症。}

高敏感性徵候群定義上一定是藥品所引起，另外要有以下情況至少三種：急性皮疹、至少侵犯一處內臟器官、至少兩處淋巴結腫大、至少一種血液異常(淋巴球太高或太低、酸性球比例或絕對值太高、血小板太低)、發燒超過 38°C。

常見引起高敏感性徵候群的藥物只有特定幾種，其中抗癲癇藥物phenytoin、carbamazepine、phenobarbital的發生率約在5000到100000分之一，且三種藥品之間常有交叉反應，也就是對其中一種藥物過敏者，也可能對其他兩種藥物過敏(18% of cases)。其他常見藥物還包括sulfonamide、dapsone、allopurinol、minocycline、gold，在台大醫院的統計上前三名用藥則是allopurinol, phenytoin, dapsone。有時DRESS產生會同時因兩藥物交互作用，如salazopyrine+ amoxicillin, allopurinol+ amoxicillin。與其他藥物疹相比，高敏感性徵候群較為遲發，常在用藥後2-6週才出現。在藥物診斷上，貼膚試驗及體外淋巴球測試都有人嘗試，但準確度及靈敏度依藥品不同而異，如epicutaneous patch test對抗癲癇藥物有幫助，但對allopurinol則無法診斷。

在病因上遺傳性解毒障礙似乎扮演一定角色，乙醯化較慢者(slow acetylator)似乎較易產生。因此在家屬中如果有人罹病，其他人也要特別小心。另外合併第六型皰疹病毒感染(HHV6)也被報告有關。There were significant differences between DRESS and SJS/TEN in the duration of drug intake before onset, the levels of IgG, IgA and IgM, the numbers of circulating white blood cell, lymphocyte, CD3+ T cell and CD8+ T cells, the serum levels of interferon-γ, and the titres of anti-herpes simplex virus IgG at onset. The difference in the pattern of immune responses shaped in part by previous and underlying viral infections at the time of drug exposure could cause a marked deviation in the pathological phenotype of severe drug eruptions

高敏感性徵候群的治療，全身性類固醇最常使用，劑量是每公斤體重0.5到1毫克，雖然可迅速控制臨床症狀，但對縮短病程則不見得有幫助，在減藥後臨床症狀常再復發，也有人推測類固醇使用會使第六型皰疹病毒感染活化。另外CMV也會增加，但EBV則下降。因此也有人建議全身性類固醇只在有肺炎或腎炎等內臟侵犯時才用藥，但對於肝臟的幫助要不確定，輕微會者則可外用類固醇。另外也有對慢性患者使用皮下干擾素注射方式，但報告不多。其他處理方式則包括皮膚護理、保溫及外用殺菌劑減少感染。在老年人紅皮症患者則要注意對心臟的負擔。

Diagnostic criteria for drug-induced hypersensitivity syndrome (DIHS) established by a Japanese consensus group

1 Maculopapular rash developing > 3 weeks after starting with a limited number of drugs
2 Prolonged clinical symptoms 2 weeks after discontinuation of the causative drug
3 Fever (> 38 °C)
4 Liver abnormalities (alanine aminotransferase > 100 U L⁻¹)^a
5 Leucocyte abnormalities (at least one present)
a Leucocytosis (> 11 × 10⁹ L⁻¹)
b Atypical lymphocytosis (> 5%)
c Eosinophilia (> 1·5 × 10⁹ L⁻¹)
6 Lymphademopathy
7 Human herpesvirus 6 reactivation

The diagnosis is confirmed by the presence of the seven criteria above (typical DIHS) or of the five (1∼5) (atypical DIHS). ^aThis can be replaced by other organ involvement, such as renal involvement.

Question	Yes	No	Do Not Know
1. Are there previous conclusive reports on this reaction?	+1	0	0
2. Did the adverse event appear after the suspected drug was administered?	+2	-1	0
3. Did the adverse event improve when the drug was discontinued or a specific antagonist was administered?	+1	0	0
4. Did the adverse event reappear when the drug was readministered?	+2	-1	0
5. Are there alternative causes that could on their own have caused the reaction?	-1	+2	0
6. Did the reaction reappear when a placebo was given?	-1	+1	0
7. Was the drug detected in blood or other fluids in concentrations known to be toxic?	+1	0	0
8. Was the reaction more severe when the dose was increased or less severe when the dose was decreased?	+1	0	0
9. Did the patient have a similar reaction to the same or similar drugs in any previous exposure?	+1	0	0
10. Was the adverse event confirmed by any objective evidence?	+1	0	0
NARANJO ALGORITHM- ADR PROBABILTY SCORE