Discussion
TEN is a severe skin condition that can be life-threatening, characterized by widespread skin rash, blistering, and detachment of the epidermis and mucous membranes, often accompanied by systemic symptoms such as dehydration, sepsis, and multiple organ failure. The majority of TEN cases are caused by drug reactions, with up to 95% of cases being attributed to drug use. Lamotrigine, carbamazepine, allopurinol, sulfonamide antibiotics, and nevirapine are some of the most commonly reported causative drugs [1, 2]. While synthetic medications are often implicated, herbal medications have also been reported as a rare cause of TEN. In this case, the patient had a history of primary Sjogren’s syndrome for nine years and had stopped all conventional therapy for at least one year before taking herbal medicine, which was suspected to be the cause of her TEN. An algorithm called ALDEN (ALgorithm of Drug causality in Epidermal Necrolysis) has been developed to help identify the causative drug in TEN[3]. Skin tests, such as patch, prick, or intracutaneous tests, may also be useful in identifying the offending drug [4]. However, in this case, the patient declined further testing to determine which herbal medication was the culprit. The patient was treated with a combination of methylprednisolone and immunoglobulin, as well as other supportive measures, including pain control, skin, mouth, and eye care, and infection prevention.
Autoimmune disease such as systemic lupus erythematosus[5, 6] and Sjögren’s syndrome[6] may be risk factors for TEN. In our case, the patient had a history of primary Sjogren’s syndrome. About half month before taking herbal drugs she presented with crops of petechiae and purpuric macules on her lower extremities, which did not disappear in the exfoliation process of TEN. The clinical picture, together with her laboratory data, were consistent with a diagnosis of HGP, which was first described by the Swedish physician Jan Gosta Waldenström in 1943[7]. He reported three cases of women with chronic relapsing purpura, hypergammaglobulinemia, an elevated erythrocyte sedimentation rate, and mild anemia. This syndrome was usually concomitant with autoimmune disease, most frequently Sjögren’s syndrome and occasionally rheumatoid arthritis or lupus erythematosus[8]. The pathogenesis of HGP remains incompletely understood. An immune dysregulation hypothesis, supported by the fact that the small circulating immune complexes containing monoclonal IgG or IgA rheumatoid factor had been isolated in individuals with a clinical presentation that fits this syndrome, were put forward to unfold the pathological mechanism [9,10]. In the case under discussion, the patient’s rheumatoid factor was 405IU/L and IgG was 25.56g/L.
A noteworthy aspect of this case is that the patient had a history of autoimmune disease, which is a known risk factor for TEN. Furthermore, she stopped her regular therapy for Sjögren’s syndrome for at least one year before taking the herbal medicine. It is possible that the immune dysregulation caused by the underlying autoimmune disease and the absence of proper medical management created an environment in which herbal medicine triggered a severe immune response, resulting in TEN.
It is essential to note that while herbal medicine is perceived as ”natural” and ”safe” by some individuals, it can have adverse effects and interact with conventional medications. The lack of regulation and standardized manufacturing processes of herbal products make it difficult to ensure their safety and efficacy. Moreover, herbal medicine use is often not disclosed to healthcare professionals, making it challenging to identify possible drug interactions and adverse effects.
In conclusion, healthcare providers should be aware of the potential adverse effects of herbal medicine use, especially in patients with underlying autoimmune diseases. Patients should be educated on the potential risks of herbal medicine use and advised to disclose all medications they are taking to their healthcare provider. A comprehensive approach that includes a thorough history, physical examination, laboratory evaluation, and skin testing can help identify the causative agent in TEN and other adverse drug reactions.