Ankur Ba ( Department of Internal Medicine, Maricopa Integrated Health System, Phoenix, AZ-85008. )
Bertram Hurowitz ( Department of Internal Medicine, Maricopa Integrated Health System, Phoenix, AZ-85008. )
Nadeem Hassan ( Department of Internal Medicine, Maricopa Integrated Health System, Phoenix, AZ-85008 )
Van Thiel DU ( Department of Internal Medicine, Maricopa Integrated Health System, Phoenix, AZ-85008 )
Abdul Nadir ( Department of Internal Medicine, Maricopa Integrated Health System, Phoenix, AZ-85008. )
Essential mixed cryoglobulinemia (EMC) is a common extra-hepatic manifestation of hepatitis C virus (HCV). Complex Regional Pain Syndrome type I (CRPS) or Reflex sympathetic dystrophy (RSD) has never been reported in association with HCV. This is the first case report of RSD in a patient with HCV related cirrhosis and EMC.
The clinical features of essential mixed cryoglobulinemia (EMC) include arthralgias, fatigue, myalgias, peripheral neuropathy, lymphadenopathy, hepatosplenomegaly, hypocomplementaemia, renal failure and cutaneous vasculitis.1,2 EMC is frequently found in patients with hepatitis C infection (HCV), but is usually not symptomatic.3,4 In the present report, typical findings of reflex sympathetic dystrophy (RSD) were observed in a professional upholster with HCV and EMC.
A 53-year-old left-handed Caucasian woman, an upholster by profession for 20 years, presented to the Maricopa Medical Center (MMC) with a three-day history of bilateral weakness of upper and lower extremities, generalized muscle aches, and subjective fevers. A year earlier, she had woken up from her sleep feeling burning pain and numbness affecting both of her hands with the left hand being worse than the right. Both hands had become progressively weak for a year but for the 6-8 weeks prior to her visit to MMC; the weakness had become so severe that she could barely grip with her left hand. Moreover, her left hand was extremely sensitive to even the slightest touch and became bright red and swollen. Her hand sensitivity was such that she could not tolerate air conditioning and resorted to covering her hand in a towel. In addition to hand sensitivity, she had diffuse joint stiffness and lower extremity weakness which resulted in difficulty with ambulation and occasional falls. Her symptoms were exacerbated with cold weather. Because of burning pain in the soles of her feet, she could not stand for more than 10-15 minutes.
Her past medical history was significant for hypothyroidism, hypertension, depression, coronary artery disease, and hepatitis C with biopsy proven cirrhosis of liver. She reported no history of trauma to her hands. She stopped drinking alcohol one year prior to her presentation and had not used intravenous drugs for 20 years. She had a 30-pack year smoking history but quit smoking 5 years prior to her current presentation.
Her vital signs were normal. She had not experienced any change in weight. Her nails were clubbed. She guarded her left hand and was extremely reluctant to be touched because of pain. She developed flexion contracture of her 3rd, 4th and 5th fingers; manifested hyper and hypopigmented skin of her finger with thickening distal to the proximal interphalangeal joints (Figure 1). She had markedly reduced sensation to the level of the wrist as well as limited motion of wrist. Her left thenar and hypothenar muscles were atrophic. Her left hand's motor strength was 3/5 compared to 5/5 on the right. The motor strength of her left proximal upper extremity and right upper as well as lower extremity was normal. Sensory loss was evident in both hands being more pronounced for the 2nd and 5th digits of the left hand and 2nd, 3rd, and 5th digits of the right hand. The patient reported a feeling of numbness and tingling in all four extremities. Her deep tendon reflexes were present. Cervical spine motion was normal without paraspinal muscle tenderness. Her lower extremities were mottled, hyperpigmented and had a macular rash (figure 3).
The hepatitis B core antibody IgG was negative. She was HCV genotype 1a with a viral load of 169, 019 IU. Albumin, total protein, total bilirubin, prothrombin time and alkaline phosphatase were normal but AST and ALT were raised at 110 (14-36 mg/dl) and 137 (0-40 mg/dL) respectively. Her TSH level was slightly elevated at 5.678 IU/ml (0.35-5.5). Cryoglobulins were positive, but anti-nuclear antibody (ANA), anti-citruline containing pepetide IgG (anti-CCP), anti-smooth muscle antibody (anti-SMA), rheumatoid factors, anti-scleroderma antibody, C3 complement, anti-Sjogren syndrome A and B (anti-SSA, anti-SSB), and HIV results were negative or within normal limits.
An abdominal ultrasound revealed normal liver, common bile duct, gall bladder and spleen. X-rays of both lower extremities revealed diffuse osteopenia. X-rays of the right upper extremity were normal, but the left upper extremity revealed a soft tissue swelling in the dorsum of the distal forearm, joint-space narrowing of the radiocarpal joint, and osteopenia (Figure 2). Electrodiagnostic studies of the left upper extremity showed no recordable response of the sensory components of median and ulnar nerves and reduced amplitudes of the motor components of median and ulnar nerves. The brachial plexus studies of the left upper extremities were normal. Electrodiagnostic studies of the right upper extremity showed slightly prolonged latency of the sensory component of the distal median nerve, but the sensory component of the ulnar nerve was normal. Studies of the motor components of both nerves in right upper extremity revealed reduced amplitude. Nerve conduction studies of both lower extremities were abnormal (left > right). CT-scan of chest and head did not show any masses or other pathology.
This case meets the criteria for reflex sympathetic dystrophy or complex regional pain syndrome type 1 (CRPS Type 1).
She was referred to physical therapy that reduced her requirement for morphine. She took herself off of Pegylated interferon and ribavirin treatment after two weeks because of the onset of chest pain.
|Figure 1. (A) Left hand of the patient showing flexion contractures of the fingers with skin changes. (B) Comparison of two hands. |
|Figure 2. Comparison of hand Xrays. |
|Figure 3. Lower extremities showing rash consistent with cryoglobulinemia. |
This patient referred here has advanced RSD, qualifying as stage III based on her clinical and neurological evaluation. The presence of burning pain and demyelinating neuropathy of the left upper extremity with trophic changes of the skin are consistent with RSD. Additional features of stage III RSD in this case include flexion contracture of her fingers & digits, severe palmar and digital muscle atrophy, decreased motor strength, limited range of motion, and osteopenia.5-8
Other potential diagnostic considerations in this case include rheumatoid arthritis, primary or metastatic cancer with a paraneoplastic syndrome and either a median or ulnar nerve entrapment syndromes. The negative ANA, anti-CCP (IgG), anti-scleroderma antibody, and rheumatoid factor are evidence against these other disease processes. In addition there is no evidence of cancer on CAT scans of head and chest as well as an ultrasound of the liver. Finally, the EMG and nerve conduction studies documented non-specific impairment in ulnar and median nerve conduction of left upper extremity that is not consistent with a focal nerve entrapment problem, but rather a polyneuropathy due to cryoglobulinemia. The diffuse neurological symptoms, lower extremity skin changes, nerve conduction studies and electromyographic evaluation all support a polyneuropathy consistent with EMC associated with HCV. In addition, the brachial plexus MRI and seven-view x-rays of spine failed to reveal any evidence for a brachial plexopathy or cervical radiculopathy.
Peripheral nerve lesions and dorsal root disorders are two important causes of RSD.8 The polyneuropathy in this patient most likely resulted from a combination of EMC and possibly some trauma occurring as a result of her occupation.9 B cell infection of HCV occurs as a consequence of virus binding to the CD 81 receptor located on B cells. This results in production of monoclonal proteins that include cryoglobulins that can be deposited in blood vessels, bones, joints, muscles, and nerves causing a focal vasculitis, arthritis/arthralgias, muscle weakness and atrophy, bone deformity, and overt neuropathy.3,4,10 Rheumatoid factor sero positivity is frequently present in patients with HCV and cryoglobulinemia.1,2 The nerve damage in HCV positive patients with cryoglobulinaemia occurs as a result of immune mediated mechanisms that include a focal vasculitis rather than a direct cytopathic effect.9,11 The treatment of RSD includes physical and occupational therapy, pain medications, sympathetic nerve block, oral prednisone, gabapentin and calcitonin.12
This is the first reported case of RSD in a patient with HCV and EMC to the best of our knowledge. A combination of HCV induced polyneuropathy occurring as a consequence of the presence of EMC and possibly heavy manual labour resulting in unintentional trauma to the left hand produced the RSD in this individual.
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