Toxic epidermal necrolysis (TEN) associated with herbal medication use in a patient with systemic lupus erythematosus

A 49-year-old woman with history of rheumatic fever necessitating mechanical mitral valve replacement and a cerebrovascular accident of presumed embolic etiology presented with several months of progressive fatigue, weakness, arthralgias, and myalgias. After an extensive workup, a rheumatologist in the community diagnosed her with systemic lupus erythematosus and dermatomyositis. The patient refused therapy with corticosteroids and disease-modifying agents, citing concerns of adverse effects. She consulted a naturopathic clinician, who gave her Rejuvenator Pills, Super Booster pill, Genesis Juice, and alkaline water (Table 1). Several weeks later, the patient developed dusky erythematous plaques on her anterior and posterior trunk, face, and proximal extremities. Over the next several weeks, she became progressively weak until she was ultimately bedbound. The plaques over her back began to denude. Upon admission to an outside hospital, she was diagnosed with warfarin-related skin necrosis, superinfected decubitus ulcers, and severe anemia. She refused blood transfusion, and was discharged home with clindamycin and iron. After her clinical status deteriorated over the subsequent week, she arrived at our hospital by ambulance. In addition to the herbal medications she had recently started, she had been taking warfarin, furosemide, nitroglycerin via skin patch, and aspirin for over 10 years. On exam, she was febrile, tachycardic, hypotensive, and toxic-appearing. Conjunctivitis was absent. Her mucous membranes were dry, with easily removable white and yellowish deposits on the buccal mucosa. No lesions or ulcerations were present. Dermatologic exam demonstrated confluent scaly, violaceous erythematous patches and plaques covering 60% of the total body surface area with focal areas that were denuded. Large areas of denuded skin were present over the back, inframammary folds, and underneath her abdominal pannus (Figures 1 and 2). Nikolsky’s sign was present. She was oriented to person only. Initial laboratory studies were significant for the following: white blood cell count 1⁄4 12,800 cells/mm, hemoglobin 1⁄4 7.3 g/dL, creatinine 1⁄4 11.2 mg/dL, blood urea nitrogen 1⁄4 136 mg/dL, and bicarbonate level 1⁄4 15 mmol/L. She was admitted to the medical intensive care unit for presumed sepsis. Aggressive resuscitation and broad spectrum antibiotics were administered. A thorough workup for infection, including blood and urine cultures, chest radiography, and lumbar puncture, was unremarkable. Antinuclear antibodies (ANAs) were present in a 1:2560 titer; with a nucleolar and speckled pattern and cytoplasmic antibodies. Additional rheumatologic workup revealed positive anti-Smith antibody and weakly positive antiribonuclear protein antibody. Pathology from a punch biopsy performed by a dermatology consultant on hospital day 2 demonstrated full-thickness skin necrosis with scant perivascular infiltrate. While the patient’s family had disposed of the pill containers, they had kept several pills. These were sent for analysis, which did not reveal contamination with heavy metals or allopathic medications. The patient was ultimately diagnosed with TEN and systemic lupus erythematosus with overlap syndrome, and intravenous methylprednisolone was administered. Broadspectrum antibiotics were administered for 48 hours, but stopped after workup for infection proved unrevealing. Wound care was mupirocin ointment with petrolatum dressings twice daily as per the hospital’s TEN protocol. The patient’s course was complicated by acidosis requiring hemodialysis and several tonic-clonic seizures, a result of presumed lupus cerebritis due to rapidly progressive lesions on serial magnetic resonance images (MRIs) with a negative lumbar puncture. Renal biopsy demonstrated acute tubular necrosis and collapsing glomerulopathy. The patient ultimately recovered, and was discharged to a rehabilitation facility. In follow-up several months later, she had healing skin with residual dyspigmentation and normal renal function. She was ambulatory and fully oriented, but complained of persistent memory difficulties.