Combination of immunotherapy and Kampo medicines for a patient with autoimmune autonomic ganglionopathy

Autoimmune autonomic ganglionopathy (AAG) is a rare autoimmune disease characterized by various autonomic symptoms and is caused by anti-ganglionic acetylcholine receptor (gAChR) antibodies. The gAChR consists of two α3 and three β4 subunits and mediates fast synaptic transmission in all peripheral autonomic ganglia in the autonomic nervous system. Most patients with AAG are treated with immunotherapy followed by oral prednisolone or immunosuppressants. No cases of AAG treated with immunotherapy combined with Kampo medicine have been reported. Herein, we report an AAG patient who showed clinical improvement after immunotherapy concurrent with saikokaryukotsuboreito (SRBT) and hochuekkito (HET). A 24-year-old woman presented with post-infection cough that first appeared nine months prior to presentation. She was admitted to our hospital because of a four-month history of orthostatic dizziness, palpitation, headache, early satiety, appetite loss, nausea, and vomiting. The patient was positive for anti-gAChRα3 antibodies (Abs) (antibody index [AI]: 1.712 [normal range < 1.0]). She was diagnosed with AAG and subsequently treated with two courses of intravenous methylprednisolone therapy (IVMP). Her autonomic symptoms and orthostatic tachycardia gradually improved, and her anti-gAChRα3 Ab serum level returned to within the normal range (AI: 0.602). However, her orthostatic dizziness, palpitations, and cough relapsed after she suffered from nephritis six months later, and she was readmitted to our hospital. Her height, weight, and body mass index were 159.8 cm, 49.7 kg, and 19.46 kg/m, respectively. Her pulse rate increased to 150 beats/min immediately after standing, and she exhibited syncope 1 min after standing. Upon admission, she presented with a wide range of autonomic symptoms related to orthostatic intolerance (OI) including lightheadedness and palpitations, dry mouth, paroxysmal coughing, decreased trunk sweating, hyperhidrosis of the palms and soles, cold hands and feet, peripheral paresthesia, nausea, vomiting, early satiety, constipation, and nocturia. She also complained of frustration and depressed mood because of chronic work stress, difficulty falling asleep, susceptibility to fatigue and cold, rare menstruation, menstrual pain and muscle cramps. The physical examination findings were: pulse signs, medium pattern; tongue signs, purple with white coating; abdominal signs, intermediate; epigastric discomfort and resistance, right hypochondriac discomfort and resistance, brisk pulsation in both the supraand para-umbilical region, right para-umbilical tenderness and resistance, and weakness of the lower abdominal region. When her anti-gAChRα3 Ab level became positive (AI: 1.359), she was treated with two courses of IVMP, followed by oral administration of 20 mg of prednisolone (PSL) per day along with 7.5 g of SRBT (TJ-12, Tsumura & Co., Tokyo, Japan) and 7.5 g of HET (TJ-41, Tsumura & Co.) (Table 1) according to the physical findings. Her OI, palpitations, and insomnia improved. After 10 months, oral PSL was tapered to 9 mg/day, and both SRBT and HET were discontinued. Six months later, PSL had been tapered to 6 mg/day, but her symptoms relapsed after common cold and an increase in work-related stress. Her anti-gAChR Ab results remained negative. We restarted SRBT at 7.5 g/day, and her symptoms improved. Based on the negative anti-gAChR Ab result, her dose of oral PSL was tapered over six months to 3 mg/day. Two months later, she exhibited low-grade fever, general fatigue, appetite loss, lightheadedness, xerostomia, and insomnia after common cold. The anti-gAChR Ab result remained negative. We then reintroduced HET treatment, which gradually improved her symptoms. Oral PSL was again tapered to a final dose of 1 mg/day after 23 months. For intractable AAG, IVMP, intravenous immunoglobulin, and/or immunoadsorption plasmapheresis are used as the first course of treatment, followed by immunosuppressive agents such as oral PSL and azathioprine. In the present case, we could not add azathioprine to PSL because of repeated infection. Instead, we used IVMP as the first-line therapy, followed by oral PSL and Kampo medicine. With this regimen, we were able to reduce the dose of PSL to 1 mg/day. We selected SRBT based on the presence of depression and insomnia and HET based on the presence of OI, mild fever, and susceptibility to fatigue and cold. Several cases have been reported involving the use of the Received: 23 October 2022 Revised: 21 December 2022 Accepted: 21 December 2022