Clinical characteristics: An 8-year-old boy from Chenzhou City, Hunan Province, China visited Sun Yat-sen Memorial Hospital of Sun Yat-sen University, China on October 29, 2020 for the first time with complaints of abnormal sensation in both feet over the past 2 years. The burning sensation and mild itching symptoms in both feet and ankles started with no obvious cause. The symptoms were not relieved by treating with topical glucocorticoids but were alleviated by soaking in iced water. Six months ago, the symptoms became worse, spreading from the ankles of the feet to the lower extremities, accompanied by burning pain, severe itching but normal skin temperature, and scattered chilblain skin lesions on both lower extremities. The patient sought the local clinics several times where he was diagnosed with allergic skin rash and treated with dioxypromazine granules, zinc oxide borate borneol ointment and naftifine ketoconazole cream. However, these treatments did not relieve the symptoms.
The patient was born prematurely at G2P2 (Gravida 2 and Pregnancies 2) and lagged behind his peers the same age in growth and development. The patient had difficulty in socialization with peers due to skin lesions on both lower extremities.
Physical examination: Normal skin temperature and ruddy skin in both lower legs with ichthyosis and lichenification, height 108 cm (<-3 SD), weight 15 kg (<-3 SD) blood pressure 148/100 mmHg, normal heart rhythm, and heart rate 156 beats/min. The patient was poorly developed and malnourished with unintentional weight loss. Skin redness and swelling on both lower extremities were visible, with focus on the ankles and feet accompanied ichthyosis and lichenification. The skin of both soles and heels and between the toes was chapped and ulcerated to form frostbite-like skin lesions (Figure 1). Two ulcer lesions were observed on the skin of the right ankle (Figure 2).
Laboratory examination: blood routine and biochemical tests were performed. White blood cell count was 13.67 x 109/L (Normal: 4.0-10.0 x 109 g/L); Red blood cell count was 4.33 x 1012/L (Normal: 4.2-6.0 x 1012 g/L); Platelet count was 474 x 109/L (Normal: 125-350 x 109 g/L); Neutrophils were 10.61 x 109/L (Normal: 1.8-6.3 x 109 g/L). Blood glucose was within the normal range. Creatine kinase was 1,662 U/L (Normal: 26-174 U/L); lactate dehydrogenase was 597 U/L (Normal: 108-252 U/L); creatine kinase isoenzyme was 103 U/L (Normal: 0-24 U/L); and uric acid was 508 mumol/L (Normal: 120-450 mumol/L). Antinuclear antibody (ANA), rheumatoid factor (RF), and antistreptolysin O (ASO) screening data were within the normal ranges.
Pathological examination: In view of this specific dermal change, we performed a skin pathological examination of the subject after admission. The pathological examination showed only mild hypertrophy of the epidermis with hyperkeratosis and mild thickening of the granular layer in the skin tissue. No obvious abnormalities in the blood vessels or nerves in the dermis or subcutaneous fat were observed.
Taken together, the patient was diagnosed PEM. SCN9A genetic testing was performed in the patient and his parents to assist in understanding the patient's disorder. Follow-up genetic verification for SCN9A was performed in his sister.