A Case of Delayed Onset Nephrogenic Systemic Fibrosis After Gadolinium Based Contrast Injection
A 56-year-old man visited our hospital with complaints of bilateral limb weakness, joint contractures of both upper and lower limbs, and whole body skin fibrosis. He had been diagnosed with chronic renal failure of an unknown cause ten years before and was recommended to undergo dialysis, which was not conducted because he refused the treatment. Nine years ago, an arteriovenous shunt was performed after emergency dialysis through catheterization of the internal jugular vein due to serious uremia accompanied by edema and fatigue. Neck pain and redness occurred on the area where the arteriovenous shunt was inserted and a cervical MRI showed an extradural abscess in the fifth and sixth cervical vertebrae. The abscess was then removed and a discectomy was performed at the C-5 and C-6 level. Despite the patient was renal insufficient, he underwent 5 cervical MRIs over the course of a year. Thereafter, he started peritoneal dialysis but due to recurrent peritonitis, he began to receive hemodialysis six years ago. Five months before his visit to our hospital, he displayed symptoms of edema of the bilateral lower limbs together with skin thickening of the bilateral upper and lower extremities. Contractures of the shoulders, wrists, hip joints, and knee and ankle joints then gradually occurred. He developed skin nodules between the first and second digit and had a gait disability due to weakness of the bilateral lower limbs and contracture of the bilateral knees. He denied any family history of such diseases other than that his mother was diagnosed with diabetes mellitus.\nIn regards to his vital signs after hospitalization, his blood pressure, pulse rate, body temperature, height, and weight were 120/70 mmHg, 70 beats per minute, 36.5℃, 170 cm and 65 kg, respectively. He appeared chronic ill looking. According to his complete blood count test, his hemoglobin was 10.7 g/dl, white blood cell count was 6,160/mm3, eosinophil was 5.8%, blood nitrogen level was 34.6 mg/dl, blood creatinine level was 5.81 mg/dl (estimated GFR at 10.1 ml/min/1.73 m2), sodium was 139 mEq/L, potassium was 4.8 mEq/L, calcium was 11.8 mEq/L, phosphorus was 6.5 mg/dl, C-reactive protein was 0.92 mg/dl, erythrocyte sedimentation rate was 62 mm/hr, creatine kinase was 49 IU/L, lactate dehydrogenase was 370 IU/L, parathyroid hormone was 332.9 pg/m, and B2-microglobulin level was 23.3 mg/dl. In the rheumatoid test, he was fluorescent antinuclear antibody positive (1 : 80). However, the results for the anti-RNP, anti-Sm, anti-SSA (Ro), anti-SSB (La), anti-Scl-70, anti-centromere antibody and anti-Jo tests were negative. The values obtained from his protein immunoassay and thyroid function test were within the normal limit range (). Electrocardiography showed a right bundle branch block and echocardiography found a slight mitral valve regurgitation, mild pulmonary arterial hypertension, and bilateral cardiomegaly. The simple chest radiography indicated no abnormal finding in the pulmonary parenchyma and the pulmonary function was found to be normal.\nThree months after development of symptoms, an electrophysiologic study was performed. Although no abnormal findings were observed in the nerve conduction study regarding the bilateral lower extremities and the right upper extremity, needle electromyography indicated positive sharp waves and a fibrillation potential in the bilateral vastus medialis, gastrocnemius, tibialis anterior, iliopsoas, and right peroneus longus. However, no abnormal spontaneous activity was noted in the bilateral first dorsal interosseous, biceps brachi, and left peroneus longus. Decreased motor unit action potentials (MUAP) were observed in the left gastrocnemius and tibialis anterior. Short-duration MUAPs were observed in the left vastus medialis, tibialis anterior, and iliopsoas and short duration polyphasic MUAPs in the right vastus medialis, gastrocnemius, and peroneus longus. With regard to muscle recruitment patterns, early recruitment was observed in the right tibialis anterior and reduced recruitment in the bilateral brachial biceps, left gastrocnemius, peroneus longus, right vastus medialis, iliopsoas, and first dorsal interosseous ().\nHistopathologic examination of the skin, fascia, and muscle tissues in the posterior right calf was performed. Histopathologic examination revealed dermal fibrosis with collagen deposition in the dermis, and septal fibrosis in the subcutaneous tissue (). Non-enhanced MRI of the bilateral lower limbs showed muscular atrophy in the bilateral gastrocnemius and an increased signal intensity in the fascia along the edge of the soleus muscle (). He was diagnosed as NSF. Although, the patient was administered 30 mg of prednisolone twice daily, his symptoms did not improve.\nOn the thirteenth day after admission, he was transferred to the department of physical and rehabilitation medicine to treat his gait disability, weakness of the bilateral lower extremities, and joint contractures of the whole limbs. He had pain whenever he moved his shoulders, elbows, hip joints, knees, and ankles, with numerical rating scale at 3 at rest and 7 in motion. During sleeping he woke up about ten times due to pain. Physical examination indicated whole body skin fibrosis and skin nodules between the first and second fingers. A manual muscle test showed that the bilateral lower limb muscles had a muscle strength grade of 4, except for the bilateral upper limb and bilateral hip joint flexor and hip extensor muscles. The bilateral upper limb and bilateral hip joint flexor and hip extensor muscles grades were 3+. A Gower's sign was also observed. Hypesthesia was not noted in a sensory examination. Limit of motion was observed in all joints of the upper and lower limbs. Knee Flexion contractures were 15 degrees for the right and left sides and ankle plantar flexion contractures were 25 degrees in the right side and 20 degrees in the left side (). Due to weakness of the bilateral lower limbs, bilateral knee flexion contractures, and ankle plantar flexion contractures, he was not able to perform an independent gait. He required moderate assistance from others when washing his face, maintaining personal hygiene, and putting on clothes because of flexion contractures of the bilateral shoulder and elbow joints. There was no abnormal finding in the deep tendon reflex, Babinski reflex, and Hoffman's reflex tests.\nFour months after he developed symptoms, he was prescribed prednisolone. After sixteen days on the medication, an electrophysiologic study revealed no abnormal spontaneous activity in the bilateral vastus medialis, gastrocnemius, tibialis anterior, iliopsoas, and right peroneus longus. In the electromyography analysis, no myopathy-like findings in the motor unit action potential were observed, except for in the right iliopsoas. Regarding the right iliopsoas, short duration polyphasic MUAPs and early recruitment pattern MUAPs were noted. Left peroneus longus, iliopsoas, right vastus medialis, and iliopsoas showed an increased MUAPs recruitment pattern relative to a previous study ().\nPhysical modalities, stretching exercise, and joint mobilization techniques were utilized to treat the joint contractures of the bilateral upper and lower limbs using paraffin on the finger to relieve finger stiffness. Training was performed to improve the activities of daily living in an occupational therapy room. He was also provided physical therapy to enhance bilateral lower limb muscle strength and improve gait function using a walker, together with independent gait training in a hydrotherapy room. During gait movement, his heels could not contact the floor due to his ankle plantar flexion contractures; therefore, outsoles were attached onto the heels so that heel contacted the floor. He received rehabilitation for a month in the department of physical and rehabilitation medicine. After this treatment, the pain in motion was reduced with an NRS of 5, and the issues associated with sleeping due to pain also improved. In addition, his finger stiffness was also alleviated. Because of the increased range of motion of the bilateral shoulder and elbow joints, he required minimal assistance from others in washing his face, maintaining personal hygiene, and putting on clothes. The modified Barthel index, which was originally 51 at the time of transfer to the department of physical and rehabilitation medicine had increased to 77 at discharge from the hospital. In addition, the bilateral lower extremity joint range of motion, bilateral knee flexion contractures and ankle plantar contractures improved by 5 degrees. When he was discharged from hospital, he was able to walk independently using a standard walker.