Advertisement
Mayo Clinic Proceedings Home

37-Year-Old Man With Back Pain

      A 37-year-old male auto mechanic was admitted to the hospital because of a 4-day history of intermittent episodes of severe left flank and low back pain. One week before admission, he had started a part-time job as an industrial painter. Each episode of the patient's pain began suddenly, reached full intensity in 10 seconds, and then resolved completely in 30 seconds. The pain had a burning quality and eventually radiated to the lateral aspect of his left thigh and into his ipsilateral groin. It reappeared every 10 to 15 minutes. The pain was not associated with postural changes, exercise, or bowel or bladder function. The patient denied having fever, chills, diarrhea, constipation, nausea, vomiting, or diaphoresis. He was initially evaluated at a local emergency department, where urinalysis revealed no hematuria. The patient received acetaminophen and codeine but had no pain relief. He was then admitted to the local hospital where he was given intravenous morphine and diazepam. He was transferred to our institution because of unrelenting pain.
      The patient's medical history was notable for systemic lupus erythematosus (SLE), diagnosed in 1978. He had experienced several flares of this disorder over the years, including recurrent episodes of pericarditis. He had been treated with prednisone (7.5 mg/d) and hydroxychloroquine. Three years earlier, deep venous thrombosis developed in his left arm and left leg, with evidence of lupus anticoagulant that justified long-term anticoagulation with warfarin. Two years earlier, azathioprine (75 mg/d) was initiated, and hydroxychloroquine was discontinued; the SLE had been well controlled with low-dose prednisone and azathioprine since then. Since the age of 10 years, the patient had had posttraumatic seizure disorder; he was treated with phenytoin and had been seizure free for the past 10 years. In addition, he had irritable bowel syndrome.
      The patient denied using alcohol or tobacco. His mother had rheumatoid arthritis.
      On physical examination, the patient had a temperature of 38.1°C, heart rate of 68/min, and blood pressure of 120/60 mm Hg. During the physical examination, he experienced acute intermittent attacks of pain that caused him to jump out of bed, screaming and crying in pain; between these paroxysms of pain, he was comfortable. Because of the radicular character of his pain, a lumbar radiculopathy due to a herniated disk was suspected.
      • 1.
        Which one of the following maneuvers or findings, if positive, is most likely to confirm the diagnosis suspected in this patient?
        • a.
          Ipsilateral straight leg raising
        • b.
          Crossed straight leg raising
        • c.
          Great toe extensor weakness
        • d.
          Impaired ankle reflex
        • e.
          Dermatomal sensory loss
      Ipsilateral straight leg raising is the most sensitive (80%) of the commonly used physical examination techniques for the detection of lumbar radiculopathy. However, to establish a diagnosis, the most specific test must be used. Crossed straight leg raising has a specificity of 90%, and a positive result is the most specific sign of lumbar radiculopathy. Ipsilateral straight leg raising and crossed straight leg raising tests are highly reproducible with inter-observer agreement of 78% and 74%, respectively. Great toe extensor weakness, impaired ankle reflex, and a dermatomal sensory loss are useful in localizing the level of the root compression but lack the sensitivity and specificity of the aforementioned tests.
      • Deyo RA
      • Rainville J
      • Kent DL
      What can the history and physical examination tell us about low back pain?.
      Findings on the rest of the physical examination were unremarkable. Specifically, no costovertebral angle tenderness was elicited. Results of the ipsilateral and crossed straight leg raising maneuvers were negative. Findings on the rest of his spine and neurologic examinations were normal. There was no sciatic notch tenderness, and the musculoskeletal examination, including that of his left lower extremity, was unrevealing.
      On admission, laboratory evaluation (reference ranges shown parenthetically) included a normal hemoglobin concentration and normal leukocyte and platelet counts. The erythrocyte sedimentation rate was 3 mm in 1 hour (0-22 mm in 1 hour), and the international normalized ratio was 2.2 (therapeutic range). The creatinine level was 1.0 mg/dL (0.8-1.2 mg/dL); urinalysis revealed no erythrocytes, and there was no hemosiderin in the urine. His anti–double-stranded DNA antibody titer was positive at 75 IU/mL (negative). Findings on anteroposterior and lateral spine radiographs were normal. Because of persistent radicular pain, magnetic resonance imaging (MRI) of the lumbar spine was performed but showed no structural abnormalities.
      • 2.
        Which one of the following diagnoses could explain the patient's condition but is most likely to be overlooked on MRI?
        • a.
          Stress fracture of the vertebral spine
        • b.
          Osteomyelitis of the vertebrae
        • c.
          Disk space infection
        • d.
          Spinal stenosis
        • e.
          Herniated lumbar disk
      Magnetic resonance imaging of the lumbar spine is a commonly used diagnostic modality in the evaluation of low back pain, but its diagnostic capabilities are frequently overestimated. The use of corticosteroids is a risk factor for the development of stress fractures of the vertebral spine because of the development of osteopenia. Computed tomography (CT) is the most accurate means of diagnosing this condition. It can demonstrate areas of sclerosis corresponding to reparative bone formation and may show cancellous or cortical discontinuity, which is not apparent on plain x-ray films. In this instance, MRI usually does not show the actual fracture but only decreased signal intensity in T1-weighted images.
      • Stroebel RJ
      • Ginsburg WW
      • McLeod RA
      Sacral insufficiency fractures: an often unsuspected cause of low back pain.
      This patient is immunosuppressed and therefore at high risk for atypical and opportunistic infections. The sensitivity of MRI for osteomyelitis is 96%, with a specificity of 93%.
      • Herzog RJ
      • Guyer RD
      • Graham-Smith A
      • Simmons Jr, ED
      Magnetic resonance imaging: use in patients with low back or radicular pain.
      Disk space infection could be found on a bone or leukocyte nuclear scan, but MRI has a high sensitivity for soft tissue tumor or infection. This patient's symptoms are unlikely to represent spinal stenosis. Although MRI is comparable to CT with myelography in defining this entity, MRI has the added advantage of being noninvasive and is able to detect uncommon causes of spinal stenosis, like cysts or tumors. Magnetic resonance imaging is more sensitive than CT in detecting early disk degeneration and has better correlation with findings of herniated disk in the operating room,
      • Herzog RJ
      • Guyer RD
      • Graham-Smith A
      • Simmons Jr, ED
      Magnetic resonance imaging: use in patients with low back or radicular pain.
      but, as previously discussed, findings on our patient's examination do not support this diagnosis.
      At this time, intravenous pyelography was performed to exclude the possibility of nephrolithiasis; results of the study were negative.
      • 3.
        At this point, which one of the following diagnoses is least likely in this patient?
        • a.
          Neuropsychiatrie lupus
        • b.
          Corticosteroid-induced psychosis
        • c.
          Herpes zoster
        • d.
          Complex regional pain syndrome
        • e.
          Malingering
      Although psychosis and seizures are the only neuropsychiatrie manifestations of lupus considered in the criteria for the classification of SLE, neuropsychiatrie lupus can manifest with virtually any neurologic disorder, focal or diffuse, and could be present in patients with no other signs of active SLE. Our patient's disabling pain with its neuropathic component could be a clue pointing toward neuropsychiatrie lupus. Corticosteroid-induced psychosis is in the differential diagnosis of neuropsychiatrie lupus and has been reported with prednisone dosages of more than 30 mg/d. Symptoms include anxiety, depression, euphoria, irritability, mania, psychosis, and insomnia but not focal pain. Corticosteroid-induced psychosis usually responds to a decrease in the daily dose of corticosteroids. Because our patient's dose of prednisone was 7.5 mg/d, corticosteroid-induced psychosis is an unlikely diagnosis. The varicella-zoster virus could reactivate in a dorsal ganglia and cause acute neuritis associated with a vesicular rash that follows a dermatomal distribution. A prodrome featuring paresthesias or painful dysesthesias may precede the appearance of the characteristic rash by 24 to 96 hours, or the rash may never appear (an uncommon condition called zoster sine herpete). Therefore, a prodrome of localized zoster or zoster sine herpete could account for the symptoms of our patient. He experienced pain on light touch in a quasider-matomal distribution (allodynia) and demonstrated pronounced overreaction (hyperpathia). A complex regional pain syndrome (or reflex sympathetic dystrophy) is compatible with our patient's symptoms, although he could recall no trauma to his left leg. Diagnosis is one of exclusion and requires the development of signs of localized sympathetic dysfunction. This patient had no history of abnormal pain behavior, and no secondary gain was evident. Nonetheless, malingering remains a possible diagnosis in a patient with a pain syndrome that is difficult to characterize.
      Nine days after the onset of pain, the patient's mental status deteriorated, and fever and severe headache developed. After reversing the anticoagulation, we obtained a sample of cerebrospinal fluid to rule out a central nervous system infection. During the lumbar puncture, we noted 2 vesicular lesions, 1 over the left buttock and 1 on the upper left lumbar region. The possibility of herpes zoster was entertained. Results of the Tzanck test and the direct fluorescent antibody test of a vesicle were positive. Within a few hours, approximately 50 vesicles developed on the patient's left buttock and lower back area. The rash progressed and eventually involved his face, trunk, and limbs. The cerebrospinal fluid findings (reference ranges shown parenthetically) included a normal glucose level, protein level of 192 mg/dL (14-45 mg/dL), and 105 nucleated cells per milliliter with 96% lymphomononuclear cells (<5 mononuclear cells per milliliter).
      • 4.
        Which one of the following is the best therapeutic option for this patient?
        • a.
          Oral acyclovir, 800 mg 5 times a day for 7 days
        • b.
          Oral famciclovir, 500 mg every 8 hours for 7 days
        • c.
          Low-dose acyclovir, 5 mg/kg intravenously every 8 hours for 5 days
        • d.
          High-dose acyclovir, 10 to 12 mg/kg intravenously every 8 hours for 7 days
        • e.
          Vidarabine, 10 mg/kg intravenously every day for 7 days
      For immunocompetent hosts with nonophthalmic herpes zoster, no treatment is necessary, especially if the lesions have been present for more than 72 hours and are limited to 1 dermatome. Candidates for oral therapy (acyclovir, famciclovir, or valacyclovir) include healthy subjects with severe pain, patients with disseminated cutaneous zoster, patients older than 60 years who have an underlying disease, and patients with ophthalmic zoster. In those with ophthalmic zoster, therapy decreases ocular complications even if it is initiated 7 days after the onset of rash.
      • Keating MR
      Antiviral agents.
      Low-dose intravenous acyclovir is indicated for immunocompetent patients with acute severe pain, especially those who are older than 60 years, are febrile, or have had pain for less than 4 days.
      • Peterslund NA
      • Scyer-Hansen K
      • Ipsen J
      • Esmann V
      • Schonheyder H
      • Juhl H
      Acyclovir in herpes zoster.
      High-dose intravenous acyclovir is used in immunocompromised hosts with dermatomal or disseminated zoster. Our patient had disseminated cutaneous herpes zoster, defined by the presence of 15 or more lesions outside the primary or adjacent dermatomes. The suspicion of central nervous system involvement is another indication for high-dose intravenous acyclovir. Vidarabine is an alternative antiviral medication indicated in patients with acyclovir-resistant varicella-zoster virus infection. In all other instances, acyclovir is better tolerated and more efficacious than vidarabine for varicella-zoster virus.
      • Shepp DH
      • Dandliker PS
      • Meyers JD
      Treatment of varicella-zoster virus infection in severely immunocompromised patients: a randomized comparison of acyclovir and vidarabine.
      Our patient was given high-dose acyclovir and experienced dramatic improvement in his general and mental status as well as a pronounced decrease in the intensity and frequency of the pain attacks. The rest of his medications remained unchanged. Results of the cerebrospinal fluid polymerase chain reaction test for the varicella-zoster virus were negative. The swab culture of the skin lesions was positive for varicella-zoster virus. There was no evidence of visceral involvement.
      Our patient continued to improve and was ultimately dismissed from the hospital after completing a 7-day course of intravenous high-dose acyclovir therapy. On follow-up evaluation 6 weeks later, the patient complained of a persistent dull ache in the area corresponding to the L5 dermatome.
      • 5.
        Which one of the following is considered a risk factor for the complication that developed in our patient?
        • a.
          Age
        • b.
          Immunocompromised state
        • c.
          Prodromal sensory symptoms
        • d.
          Administration of antiviral therapy
        • e.
          Failure to treat herpes zoster with added prednisone
      Postherpetic neuralgia is the most commonly reported complication of herpes zoster, affecting 8.4% of all patients. This complication is more frequent in elderly patients. The risk increases with age, but the influence of our patient's immune status remains unclear. His clinical course began with pain and hyperesthesia in a lumbosciatic distribution. The presence of sensory symptoms during the prodromal phase of herpes zoster is a risk factor for the development of postherpetic neuralgia.
      • Choo PW
      • Galil K
      • Donahue JG
      • Walker AM
      • Spiegelman D
      • Platt R
      Risk factors for postherpetic neuralgia.
      Acyclovir and corticosteroids are frequently used to reduce the occurrence or severity of postherpetic neuralgia, but their efficacy has not been established.

      DISCUSSION

      Low back pain is one of the most frequent diagnoses made by primary care physicians, surpassed only by upper respiratory tract infections. Nine of 10 persons experience simple acute back pain at some point in their lives, and it resolves in 6 weeks in 75% to 90% of patients; however, recurrence rates are high. Current guidelines require a history and physical examination to detect conditions that could predict a complicated course. These “red flags” include age older than 50 years at first episode of back pain, history of malignancy, history of intravenous drug use, corticosteroid use, fever, weight loss, adenopathy, hematuria, signs or symptoms of systemic disease, sciatica, neurologic deficit on examination, and history of severe acute trauma. Patients with acute low back pain who have no complicating conditions have simple low back pain. Further testing is not currently recommended within the first 6 weeks of pain in this group.
      • Wipf JE
      • Deyo RA
      Low back pain.
      Our patient had multiple red flags at presentation—history of a systemic disease, long-term corticosteroid use, and a thrombophilic state while receiving anticoagulation—prompting a diagnostic work-up.
      Neuropsychiatrie lupus is difficult to diagnose because of its protean manifestations; vasculitis, mononeuropathy, transverse myelitis, cord infarcts, and meningitis are possible in addition to psychosis. This disorder can affect up to 75% of patients with SLE and, when severe, is associated with high morbidity and mortality. Its cause is associated with vascular injury. The differential diagnosis includes metabolic, pharmacological, infectious, or neoplastic etiologies as well as primary neurologic and psychiatric disorders. Imaging studies and tissue biopsy are of little clinical value because of poor correlation with clinical manifestations. Treatment depends on the underlying mechanism. Some ischemic events could be associated with the lupus anticoagulant-antiphospholipid antibody syndrome. This entity is known to cause arterial and venous thrombosis. If the lupus anticoagulant-antiphospholipid antibody syndrome were present, anticoagulation would be the mainstay of therapy. If the manifestations are mainly psychiatric, anxiolytics, antidepressants, and neuroleptic agents could be used. Otherwise, high-dose corticosteroids or cyclophosphamide would be considered in patients with major, disabling, or recurrent manifestations of neuropsychiatrie lupus or in patients who do not respond to symptomatic medication.
      Although the possibility of herpes zoster was entertained in our patient, it was not a serious consideration until the rash appeared. In imrnunocompromised hosts, cutaneous zoster can manifest with a disseminated rash, as in our patient. The rash can also be atypical (coalescent rash, hemorrhagic bullae, epidermal necrosis, black eschars, or hyperkeratotic lesions) or absent (zoster sine herpete). The rash can be especially atypical in patients with the acquired immunodeficiency syndrome. The clinician should be alert to the possibility of visceral involvement in patients with disseminated disease. Visceral zoster can manifest as encephalitis with disabling strokes and blindness, as renal failure, in association with the syndrome of inappropriate antidiuretic hormone (by multiple proposed mechanisms), and, more commonly, as varicella pneumonitis, a potentially fatal condition. The treatment of herpes zoster is high-dose intravenous acyclovir.
      Treating postherpetic neuralgia has been frustrating for both patients and physicians. Treatment has traditionally included analgesics, tricyclic antidepressants, and anticonvulsants. Little or no evidence exists concerning efficacy. Preventing postherpetic neuralgia with the use of antivirals or anti-inflammatory agents has also proved to be a challenge. Most studies addressing the use of acyclovir and prednisone are of poor quality, are of brief duration, or have enrolled few patients. A systematic review of 8 trials and 900 patients failed to demonstrate any difference at 6 months between patients who did and did not receive acyclovir.
      • Lancaster T
      • Silagy C
      • Gray S
      Primary care management of acute herpes zoster: systematic review of evidence from randomized controlled trials.
      Two clinical trials in the internal medicine literature and a population study found no significant benefit in treating herpes zoster with prednisone to prevent postherpetic neuralgia.
      • Lancaster T
      • Silagy C
      • Gray S
      Primary care management of acute herpes zoster: systematic review of evidence from randomized controlled trials.
      • Whitley RJ
      • Weiss H
      • Gnann Jr, JW
      • et al.
      National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Acyclovir with and without prednisone for the treatment of herpes zoster: a randomized, placebo-controlled trial.
      • Wood MJ
      • Johnson RW
      • McKendrick MW
      • Taylor J
      • Mandal BK
      • Crooks J
      A randomi zed trial of acyclovir for 7 day s or 21 days with and without prednisolone for treatment of acute herpes zoster.
      Our case illustrates several important considerations. The initial difficulty in making a diagnosis was due to the prolonged neurologic prodrome before the appearance of the rash. Herpes zoster must be considered when patients have radicular signs and symptoms in the absence of structural lesions or underlying diseases such as diabetes. Atypical or severe manifestations may occur in imrnunocompromised patients. The clinicians involved with this patient may have been tempted to bring early diagnostic closure to his complaints by ascribing all his symptoms with few clinical signs to a psychiatric cause. However, the presence of SLE, anticoagulation, and immunosuppression mandated a broader differential diagnosis. After appropriate diagnosis and treatment, the challenge continued because of the development of postherpetic neuralgia, a debilitating complication for which effective prophylactic and therapeutic interventions are urgently needed.

      ACKNOWLEDGMENTS

      We gratefully acknowledge the assistance of Drs Randall S. Edson and Robert M. Valente during preparation of the submitted manuscript.

      REFERENCES

        • Deyo RA
        • Rainville J
        • Kent DL
        What can the history and physical examination tell us about low back pain?.
        JAMA. 1992; 268: 760-765
        • Stroebel RJ
        • Ginsburg WW
        • McLeod RA
        Sacral insufficiency fractures: an often unsuspected cause of low back pain.
        J Rheu-matol. 1991; 18: 117-119
        • Herzog RJ
        • Guyer RD
        • Graham-Smith A
        • Simmons Jr, ED
        Magnetic resonance imaging: use in patients with low back or radicular pain.
        Spine. 1995; 20: 1834-1838
        • Keating MR
        Antiviral agents.
        Mayo Clin Proc. 1992; 67: I60-178
        • Peterslund NA
        • Scyer-Hansen K
        • Ipsen J
        • Esmann V
        • Schonheyder H
        • Juhl H
        Acyclovir in herpes zoster.
        Lancet. 1981; 2: 827-830
        • Shepp DH
        • Dandliker PS
        • Meyers JD
        Treatment of varicella-zoster virus infection in severely immunocompromised patients: a randomized comparison of acyclovir and vidarabine.
        N Engt J Med. 1986; 314: 208-212
        • Choo PW
        • Galil K
        • Donahue JG
        • Walker AM
        • Spiegelman D
        • Platt R
        Risk factors for postherpetic neuralgia.
        Arch Intern Med. 1997; 157: 1217-1224
        • Wipf JE
        • Deyo RA
        Low back pain.
        Med Clin North Am. 1995; 79: 231-246
        • Lancaster T
        • Silagy C
        • Gray S
        Primary care management of acute herpes zoster: systematic review of evidence from randomized controlled trials.
        Br J Gen Pract. 1995; 45: 39-45
        • Whitley RJ
        • Weiss H
        • Gnann Jr, JW
        • et al.
        National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Acyclovir with and without prednisone for the treatment of herpes zoster: a randomized, placebo-controlled trial.
        Ann Intern Med. 1996; 125: 376-383
        • Wood MJ
        • Johnson RW
        • McKendrick MW
        • Taylor J
        • Mandal BK
        • Crooks J
        A randomi zed trial of acyclovir for 7 day s or 21 days with and without prednisolone for treatment of acute herpes zoster.
        N Engl J Med. 1994; 330: 896-900