Choi T S, Doh K S, Kim S H, Jang M S, Suh K S, Kim S T
Department of Dermatology, Kosin Medical College, 34 Amnam-Dong, Suh-ku, Pusan, 602-702, South Korea.
Br J Dermatol. 2003 Apr;148(4):730-6. doi: 10.1046/j.1365-2133.2003.05305.x.
Pseudolymphoma syndrome (PLS) is relatively rare but can lead to death if there are extensive skin lesions, severe hepatitis, agranulocytosis and neutropenia. PLS may also give rise to harmful effects if misdiagnosed as malignant lymphoma and patients with PLS are treated unnecessarily with chemotherapy, because it may mimic histologically other lymphomas, including mycosis fungoides (MF).
To examine the clinicopathological and genotypic features of anticonvulsant-induced PLS. Patients and methods We retrospectively reviewed clinical, laboratory and histological findings for eight cases of anticonvulsant-induced PLS, and performed T-cell receptor gene rearrangement using polymerase chain reaction with paraffin-embedded specimens from each case.
The causative agents were carbamazepine (four cases), phenytoin (two cases), phenobarbital (one case) and valproic acid (one case). A cross-reaction between phenobarbital and phenytoin was observed in one case. The duration from the start of anticonvulsant therapy to skin eruption was 3-24 weeks (mean 7 weeks). The skin lesions were generalized maculopapular eruptions in all cases, including one case accompanied by vesiculopustular lesions. The frequencies of the associated features were as follows: facial oedema (88%), fever (75%), lymphadenopathy (63%), and hepatomegaly (25%). Laboratory findings revealed leukocytosis, atypical lymphocytes, eosinophilia, monocytosis, neutrophilia, lymphocytosis and abnormal liver function. Histopathologically, there was similarity between PLS and MF in that epidermotrophism of atypical lymphocytes (100%) and Pautrier's microabscess-like structures (38%) were observed. However, PLS has some differences from MF that include moderate to marked spongiosis (75%), necrotic keratinocytes (63%), and infiltration of eosinophils (25%) in the epidermis and, in the dermis, papillary dermal oedema (100%), extravasated erythrocytes (100%), lymphocytes within the dermis larger than those within the epidermis (63%), and infiltration of various inflammatory cells including neutrophils (50%). Genotypic analysis demonstrated a rearrangement of the T-cell receptor-gamma gene in one of eight cases studied. There were no deaths and all cases were improved at 2-9 weeks (mean 6 weeks), after the cessation of causative agents, systemic and topical corticosteroid therapy, and symptomatic therapy. There were no significant differences in clinical, laboratory and histological findings between the causative agents.
PLS may show histopathological findings similar to MF and take a prolonged course even after the cessation of causative agents. Thus, a clear understanding and diagnosis of this disease is considered to have an important effect on treatment and prognosis.
假性淋巴瘤综合征（PLS）相对罕见，但如果出现广泛的皮肤病变、严重肝炎、粒细胞缺乏症和中性粒细胞减少症，可能会导致死亡。如果PLS被误诊为恶性淋巴瘤，患者接受不必要的化疗，也可能产生有害影响，因为它在组织学上可能类似于其他淋巴瘤，包括蕈样肉芽肿（MF）。
研究抗惊厥药诱发的PLS的临床病理和基因特征。患者和方法我们回顾性分析了8例抗惊厥药诱发的PLS的临床、实验室和组织学检查结果，并使用聚合酶链反应对每例石蜡包埋标本进行T细胞受体基因重排检测。
致病药物分别为卡马西平（4例）、苯妥英（2例）、苯巴比妥（1例）和丙戊酸（1例）。1例观察到苯巴比妥与苯妥英之间的交叉反应。从开始抗惊厥治疗到出现皮疹的时间为3 - 24周（平均7周）。所有病例的皮肤病变均为全身性斑丘疹，其中1例伴有水疱脓疱性病变。相关特征的发生率如下：面部水肿（88%）、发热（75%）|、淋巴结病（63%）和肝肿大（25%）。实验室检查发现白细胞增多、非典型淋巴细胞、嗜酸性粒细胞增多、单核细胞增多、中性粒细胞增多、淋巴细胞增多及肝功能异常。组织病理学上，PLS与MF有相似之处，表现为非典型淋巴细胞亲表皮性（100%）和Pautrier微脓肿样结构（38%）。然而，PLS与MF也有一些不同，包括中度至明显的海绵形成（75%）、坏死角质形成细胞（63%）以及表皮中嗜酸性粒细胞浸润（25%），在真皮中，乳头真皮水肿（100%）、红细胞外渗（100%）、真皮内淋巴细胞大于表皮内淋巴细胞（63%）以及包括中性粒细胞在内的各种炎症细胞浸润（50%）。基因分析显示，在研究的8例病例中有1例T细胞受体γ基因重排。无一例死亡，所有病例在停用致病药物、全身和局部使用糖皮质激素治疗及对症治疗后2 - 9周（平均6周）病情好转。致病药物之间在临床、实验室和组织学检查结果上无显著差异。
PLS可能表现出与MF相似的组织病理学表现，即使在停用致病药物后病程仍会延长。因此，对这种疾病的清晰认识和诊断被认为对治疗和预后有重要影响。
