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.