Atypical Herpetic Reactivation and Chronic Pediatric Pain
Medically unexplained chronic pain (i.e. pain persisting for more than three months) is a common problem in patients.1,2 Three cases of otherwise healthy children (two females aged 13 and 15 and one male aged 10) with medically unexplained, severely disabling pain are presented in the following sections. In all three cases, patients had severe, disabling pain of more than one year’s duration, and thorough medical evaluations were negative. Prior to developing pain syndromes, these patients were healthy children and free of medical co-morbidities or any other apparent contributing psychosocial factors. These young patients were referred to an outpatient Rehabilitation Medicine setting by their pediatrician and/or other pediatric sub-specialists. All had previous extensive medical evaluations that had not identified the cause of their chronic pain syndromes.
All three children had very high IgG titers to at least one of the herpetic viruses and had a history of childhood chicken pox and had never received vaccination to varicella. A classic vesicular outbreak in a radicular distribution was not present in any of these children. Atypical herpetic presentations have been noted before in the literature.3-9 A presumed diagnosis of herpetic reactivation was based on an extensive negative medical workup and the presence of significantly elevated IgG antibody titers to HSV I and/or varicella zoster.
A 13 year-old female was referred for evaluation of severe burning pain of 1.2 years duration in the neck and back areas rendering her increasingly immobile and unable to participate in normal activities of daily living. She was in good health prior to injuring her left knee 14 months earlier. Within two to three weeks of the left knee injury, she developed flu-like symptoms and more severe left knee pain and swelling. Her pain symptoms gradually generalized to include pain in the neck, upper extremities, low back, and lower extremities and she developed generalized fatigue. She developed painful vesicles in the mouth and oropharynx which interfered with eating and resulted in anorexia, severe weight loss, and hospitalization.
Prior to referral, she had been evaluated and treated by multiple medical specialties including rheumatology, orthopedic surgery, dermatology, psychiatry, psychology, and physical medicine.
The prior workup included:
Prior treatment included a two week course of acyclovir that had not altered the symptoms (her mother could not recall dosage or frequency of administration.)
On initial physiatry examination at 14 months post injury, this patient had diffuse tightness and tenderness in the muscles of the neck, shoulders, low back and hips with multiple foci of muscle contraction. She was able to stand and briefly walk in an abnormal gait pattern due to guarding from pain. She spent her day lying in bed, sitting in a comfortable chair, or being pushed in a manual wheelchair by her mother. Her neurological exam was normal with respect to reflexes and motor strength but she had severe hyperalgesia to pinprick over the skin of the neck, back, upper and lower extremities.
Also present were:
Given the negative medical work up, the presence of herpetic-appearing vesicles in the throat coupled with hyperalgesia, painful rash, and enlarged lymph nodes, a diagnosis of herpetic reactivation was postulated. IgM and IgG viral antibody titers for varicella zoster, herpes simplex 1 and 2 were measured. IgG to varicella zoster was elevated (see Table 1). The patient was started on acyclovir 400mg 3 times per day. There was mild to moderate improvement at this dosage. After three to four weeks of treatment, the dosage was increased to 400mg of acyclovir five times per day.
After eight weeks of treatment, the oropharyngeal pain and vesicles and the erythematous rash over the left buttock and thigh had resolved. The patient had been able to resume eating and her weight had normalized. She continued to have pain in the neck, back and extremities, which was improving slowly.
After approximately eight weeks of treatment with anti-viral medication, a four-week inpatient acute rehabilitation program was initiated. The inpatient treatment program was followed by eight weeks of outpatient physical therapy. By the end of the course of outpatient physical therapy, this patient was cautiously ambulating without assistive devices. She continued to slowly improve and re-mained on 400mg acyclovir five times per day.
The last time she was evaluated, at twelve months after initiation of anti-viral therapy, the patient’s pain had significantly improved. She was eating normally, walking without assistive devices and able to return to school. The patient and her family moved and she was lost to follow-up.
A 15 year-old female was referred for evaluation of progressively increasing musculoskeletal pain of several years duration involving the neck, back, chest wall, and upper and lower extremities. She described frequent rashes accompanied by itching or burning sensations over the arms and thighs. There was no history of trauma or other known precipitating causes for this pain. She had been quite active in sports, participating in softball and basketball until six months prior to her physiatry evaluation, when all sports activity ceased due to pain.
“All three children had very high IgG titers to at least one of the herpetic viruses and had a history of childhood chicken pox and had never received vaccination to varicella.”
She had recurrent ear infections and sore throats, leading to a tonsillectomy at age 8, placement of bilateral myringotomy tubes at age 9, and adenoidectomy at age 10. Frequent bouts of nausea, vo-miting, and abdominal pain over two years’ time led to cholecystectomy at age 13 without relief of her symptoms. She was using an inhaler daily for seasonal and environmental allergies.
A complete cardiac workup for chest pain and cardiac palpitations was negative.
She was being treated for possible mild ADHD and depression without psychiatric medication. Over the course of her illness, she had been seen and evaluated by multiple medical specialties including gynecology, orthopedic surgery, dermatology, gastroenterology, allergy, pediatric cardiology, and a pediatric developmental specialist. Although previously active in several sports, she had not participated for the six months prior to her referral due to increasing neck, back, and upper extremity pain.
On initial physical examination there was:
IgG and IgM antibody titers were measured (See Table 1). IgG to Herpes Simplex 1 was extraordinarily elevated, varicella was extremely elevated, and Epstein-Barr IgG titer was mildly elevated.