Giant cell arteritis

Opinion statement Patients with a suspected diagnosis of giant cell arteritis (GCA) should be started on high-dose corticosteroid therapy without delay. A temporal artery biopsy should be performed after initiation of therapy to confirm the diagnosis. Patients with acute visual or neurologic symptoms present a neuro-ophthalmic emergency. Therapy should be initiated immediately with high-dose intravenous methylprednisolone sodium succinate and followed by high-dose oral prednisone. Treatment may begin with highdose oral prednisone in patients without visual or neurologic symptoms. Calcium, vitamin D, and peptic ulcer prophylaxis should accompany steroid therapy, as indicated. The following treatments should be considered for patients with suspected GCA and acute visual or neurologic signs or symptoms: intravenous methylprednisolone sodium succinate (250 mg intravenously every 6 hours) should be given for 3 days, followed by oral prednisone (80 mg per day or 1 mg/kg) for 4 to 6 weeks. Prednisone should then be tapered by 10 mg per day every month. Most patients require 1 year of therapy to avoid relapse. Taper and duration should be modified according to erythrocyte sedimentation rate, C-reactive protein, and signs and symptoms of GCA. Rheumatologic consultation and follow-up is often helpful for these patients. For patients with suspected GCA and no acute visual or neurologic signs or symptoms, therapy may begin directly with oral prednisone (80 mg per day or 1 mg/kg) with same taper and duration based on laboratory values and clinical signs and symptoms.     

Vasculitis working group: Selected unanswered questions related to giant cell arteritis and anti-neutrophil cytoplasmic antibody-associated vasculitis

Evidence to guide assessment and management of patients with vasculitis is lacking for many important clinical questions. The evidence surrounding several common questions about management of vasculitis was reviewed. Patients with giant cell arteritis (GCA) are at risk for developing extra-cranial large vessel inflammation. Clinicians should be aware of this complication and search for large vessel involvement in patients with GCA who have ischemic symptoms. Research is needed to define optimal strategies to identify patients with such complications. Because of the hazards of chronic corticosteroid use, alternative therapies for patients with GCA have been sought but thus far no clear alternatives have been identified. Anti-neutrophil cytoplasmic antibodies (ANCA) are associated with small-vessel vasculitis, including Wegener's granulomatosis and microscopic polyangiitis, but changes in ANCA titers should not be used as a surrogate biomarker for disease activity. Several immunosuppressive agents can be used for maintenance therapy after induction of remission in patients with ANCA-associated vasculitis, with no firm evidence that one agent is superior to others. Collectively, this review shows that more research is needed to provide a firmer body of evidence to support clinical decision-making for patients with vasculitis.     

Aortic involvement in giant cell arteritis: current data

Aortitis due to giant cell arteritis (GCA) is rare but probably underestimated given the frequent paucity of symptoms. Thus, early studies relied on the occurrence of complications to estimate the prevalence of GCA aortitis. With this method, aortitis was a feature in 3 to 18% of GCA patients. Since then, the introduction of modern imaging techniques has established that aortitis is more common than previously thought. Aortitis should be considered in patients with atypical clinical presentations of GCA consisting, for instance, in isolated laboratory evidence of systemic inflammation or a relapse during treatment. Aortitis may be difficult to diagnose, as temporal artery biopsy has limited sensitivity in patients with predominant large-vessel involvement. Positron emission tomography (PET) and magnetic resonance imaging (MRI) are both highly effective for the early diagnosis of aortitis. Case-series evaluating PET in patients with GCA found evidence of aortitis in over half the cases, with predominant involvement of the thoracic aorta. To date, no evidence is available about the potential usefulness of PET or MRI in monitoring patients with GCA aortitis over time. Involvement of the aorta and other large arteries does not change the treatment strategy, which rests on corticosteroid therapy. Administration of a corticosteroid-sparing drug should be considered, most notably when a relapse occurs. Aortitis is associated with an increased risk of aneurysm of the thoracic aorta. Consequently, all GCA patients should be monitored for aneurysm at regular intervals, even after treatment discontinuation. The recommended strategy is an annual evaluation including a chest radiograph, echocardiogram, and abdominal Doppler sonogram; these imaging studies can be replaced by contrast-enhanced computed tomography of the chest and abdomen.     

Giant cell arteritis

Opinion statement Diagnosis and management of giant cell (temporal) arteritis (GCA) should be performed by physicians who can accurately monitor the ophthalmologic, neurologic, and systemic sequelae of the disease as well as the numerous side effects of systemic corticosteroids, which are typically necessary for treatment. When the diagnosis of giant cell arteritis is seriously entertained, early treatment with adequate doses of oral or intravenous corticosteroids should not be delayed until laboratory confirmation has been obtained. Unilateral or bilateral temporal artery biopsy should be performed on all patients with suspected GCA. A positive biopsy result mandates that higher doses of corticosteroids be used during the first 2 months, which comprise the critical period for risk of new ocular ischemia. A definitive, biopsy-proven diagnosis requires at least 6 months, and typically 12 months, of corticosteroid therapy. Common pitfalls include increasing the dose and prolonging the use of corticosteroids in response to increases in the erythrocyte sedimentation rate (ESR) unrelated to GCA or visual blurring that may be related to benign tear film abnormalities, corticosteroidinduced lens changes, and other ophthalmic conditions. The muscle stiffness of polymyalgia rheumatica (PMR) must be distinguished from the osteoarthritis and other painful conditions common in the elderly. After corticosteroid therapy has begun, continuing ophthalmologic evaluation is necessary to evaluate the effectiveness of treatment and whether ocular complications, such as glaucoma or cataract, develop. Careful attention must be given to early detection and prevention of systemic side effects of corticosteroid treatment. Patients may be given gastrointestinal protective agents, such as histamine (H2)-blocking agents; vitamin D and calcium; oral hypoglyce mic agents; and, if necessary, insulin and antihypertensive drugs. If bone density measurements warrant, hormones/supplementation to prevent or reverse osteoporosis may be prescribed. After the initial diagnosis and first 4 weeks of treatment, elevation of the ESR or Creactive protein alone should generally not be used as signs of disease activity nor as a reason to increase the daily dose of steroids. If symptoms or signs of disease activity occur, the dose should be raised regardless of test results. Even with vigorous physicianpatient education, however, a patient is occasionally unable to provide adequate historical information about response to therapy, and the physician is forced to rely on laboratory values as a measure of disease activity. After initial high-dose corticosteroid therapy, patients without a classic history and wit negative biopsy results will generally receive a rapid taper to low doses of corticosteroids. The role of repeated temporal artery biopsy in the clinical management of GCA is unclear. Despite persistence of PMR and, in some cases, histologic evidence of inflammation in temporal arteries, patients do not frequently have recurrence of symptomatic GCA after 6 months or more of corticosteroid therapy. Under these circumstances, late vision loss is rare.     

A safety review of long-acting beta2-agonists in patients with asthma

Inhaled corticosteroids are the mainstay of asthma therapy; however, inhaled long-acting beta2-agonists (LABAs) are frequently used in the treatment of patients with asthma. LABAs are combined with high-dose inhaled corticosteroids (ICSs) for patients with severe persistent asthma, and they are combined with low-dose ICSs for patients older than 5 years with moderate persistent asthma. Recent safety concerns raised by data from the Salmeterol Multi-Center Research Trial (SMART) have indicated that use of LABAs in some populations may contribute to increased mortality. These concerns are warranted when LABAs are used as monotherapy in the treatment of patients with asthma in whom they may cause increased exacerbations, blunting of rescue-medication effect, and worsening symptoms. However, when used in combination with an ICS, they decrease both rescue-medication use and symptoms, increase lung function, and act as steroid-sparing agents.     

Clinical features of polymyalgia rheumatica and giant cell arteritis

Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are inflammatory diseases that typically affect white individuals >50 years. Women are affected ～2-3 times more often than men. PMR and GCA occur together more frequently than expected by chance. The main symptoms of PMR are pain and stiffness in the shoulders, and often in the neck and pelvic girdle. Imaging studies reveal inflammation of joints and bursae of the affected areas. GCA is a large-vessel and medium-vessel arteritis predominantly involving the branches of the aortic arch. The typical clinical manifestations of GCA are new headache, jaw claudication and visual loss. PMR and GCA usually remit within 6 months to 2 years from disease onset. Some patients, however, have a relapsing course and might require long-standing treatment. Diagnosis of PMR and GCA is based on clinical features and elevated levels of inflammatory markers. Temporal artery biopsy remains the gold standard to support the diagnosis of GCA; imaging studies are useful to delineate large-vessel involvement in GCA. Glucocorticoids remain the cornerstone of treatment of both PMR and GCA, but patients with GCA require higher doses. Synthetic immunosuppressive drugs also have a role in disease management, whereas the role of biologic agents is currently unclear.     

Cervical headache

Headache presents a diagnostic challenge for the physical therapist due to similarities of signs and symptoms among the many types of headache. Effective treatment depends upon accurate diagnosis and identifying the factors that may precipitate or perpetuate the symptoms. This commentary overviews some common forms of headache and specifically addresses cervical headache as a possible beneficiary of physical therapy intervention. Details of the history and physical examination, which is designed to diagnose cervical headache and rule out potential serious pathologies, are presented. Guidelines for treatment of articular and myofascial dysfunction are presented. A case report illustrating principles of examination, inherent ambiguities in diagnosis, and successful treatment is also presented.     

Postdural puncture headache in obstetrics

Postdural puncture headache is the most common major complication following neuraxial anesthesia; this adverse event is particularly frequent in obstetrics. The headache is usually benign and self-limited but if left untreated can lead to more serious complications that may be life-threatening. Many treatments and prophylactic measures have been suggested, but evidence supporting them is scarce in many cases. After accidental dural puncture the only effective preventive measure is to leave the catheter inside the dura; epidural morphine infusion may also help. Once symptoms begin, treatment is conservative for the first 24 hours. If this approach fails, the most effective intervention continues to be a blood patch, which should not be delayed beyond 24 to 48 hours in order to avoid suffering. If more blood patches are required, other possible causes of headache should be ruled out.     

Current Treatment Options: Headache Related to Menopause—Diagnosis and Management

Purpose of review

Menopause is a life-changing event in numerous ways. Many women with migraine hold hope that the transition to the climacteric state will coincide with a cessation or improvement of migraine. This assumption is based mainly on common lay perceptions as well as assertions from many in the healthcare community. Unfortunately, evidence suggests this is far from the rule. Many women turn to a general practitioner or a headache specialist for prognosis and management. A natural instinct is to manipulate the offending agent, but in some cases, this approach backfires, or the concern for adverse events outweighs the desire for a therapeutic trial, and other strategies must be pursued. Our aim was to review the frequency and type of headache syndromes associated with menopause, to review the evidence for specific treatments for headache associated with menopause, and to provide management recommendations and prognostic guidance.

Recent findings

We reviewed both clinic- and population-based studies assessing headache associated with menopause. Headache in menopause is less common than headache at earlier ages but can present a unique challenge. Migraine phenotype predominates, but presentations can vary or be due to secondary causes. Other headache types, such as tension-type headache (TTH) and cluster headache (CH) may also be linked to or altered by hormonal changes. There is a lack of well-defined diagnostic criteria for headache syndromes associated with menopause. Women with surgical menopause often experience a worse course of disease status than those with natural menopause. Hormonal replacement therapy (HRT) often results in worsening of migraine and carries potential for increased cardiovascular and ischemic stroke risk. Estrogen replacement therapy (ERT) in patients with migraine with aura (MA) may increase the risk of ischemic stroke; however, the effect is likely dose-dependent. Some medications used in the prophylaxis of migraine may be useful in ameliorating the vasomotor and mood effects of menopause, including venlafaxine, escitalopram, paroxetine, and gabapentin. Other non-medication strategies such as acupuncture, vitamin E, black cohosh, aerobic exercise, and yoga may also be helpful in reducing headache and/or vasomotor symptoms associated with menopause.

Summary

The frequency and type of headache associated with menopause is variable, though migraine and TTH are most common. Women may experience a worsening, an improvement, or no change in headache during the menopausal transition. Treatment may be limited by vascular risks or other medical and psychiatric factors. We recommend using medications with dual benefit for migraine and vasomotor symptoms including venlafaxine, escitalopram, paroxetine, and gabapentin, as well as non-medication strategies such as acupuncture, vitamin E, black cohosh, aerobic exercise, and yoga.If HRT is pursued, continuous (rather than cyclical) physiological doses should be used, transdermal route of administration is recommended, and the patient should be counseled on the potential for increased risk of adverse events (AEs). Concomitant use of a progestogen decreases the risk of endometrial hyperplasia with ERT. Biological mechanisms are incompletely understood, and there is a lack of consensus on how to define and classify headache in menopause. Further research to focus on pathophysiology and nuanced management is desired.

     

Menstrual migraine

Opinion statement The initial treatment of menstrual migraine (MM) should be the same as that of migraine that occurs at any other time during the month and should include lifestyle modifications and the use of appropriate acute therapies aimed at decreasing attack symptoms, duration, and disability. If results of acute therapy are incomplete or unsatisfactory, then preventive strategies may be required. Comorbidities may, however, influence choice of preventive therapy or accelerate initiation of preventive therapy. Comorbid dysmenorrhea, menometrorrhagia, and endometriosis argue for early use of hormonal therapies. Hormonal strategies may be appropriate because the premenstrual decline in estradiol concentration predictably precipitates MM, and targeting and preventing this decline can decrease headache occurrence. Continuous combined hormonal contraceptives can reduce hormone fluctuations and, for some MM sufferers, can deliver more than contraceptive benefits. Nonsteroidal anti-inflammatory drugs are appropriate for treatment of co-occurring dysmenorrhea or when hormonal strategies are contraindicated; their efficacy may be caused partly by the role of prostaglandins in MM and dysmenorrhea. As with the use of hormonal therapy, use of nonsteroidal anti-inflammatory drugs allows for treatment of breakthrough headache with triptans. Results of clinical trials suggest that daily use of triptans in the menstrual window may bring about as much as 50% reduction in headache frequency, but such use still requires acute treatment of breakthrough headache and adherence to daily triptan limits. Use of this strategy requires that headache occurrence be highly predictable.     

Therapeutic approach to giant cell arteritis

Giant cell arteritis (GCA) affects middle-sized or large arteries in individuals over 50 years of age. GCA is characterized by a combination of focal inflammation responsible for arterial stenosis or occlusion and of systemic inflammation manifesting as polymyalgia rheumatica, a decline in general health, and inflammatory anemia. In addition to the typical involvement of the branches of the external carotid arteries, relatively common sites of involvement include the aorta, most notably in its thoracic segment, and the subclavian, axillary, brachial, vertebral, and femoral arteries. The treatment of GCA rests on daily glucocorticoid administration, which should be started on an emergency basis in patients with incipient visual impairments (diplopia or amaurosis fugax). The duration of glucocorticoid therapy is unpredictable and side effects are common. Initial megadose glucocorticoid therapy does not decrease subsequent glucocorticoid requirements. Glucocorticoid therapy regulates the Th17 pathway, which is involved in the prominent vascular and systemic manifestations; but not the Th1 pathway, which may underlie the chronic course of the disease (whereas aspirin, in addition to decreasing platelet aggregation, blocks the Th1 mediator interferon-gamma). Although GCA is classically described as resolving within 1 to 3 years, clinical practice often teaches otherwise. Many patients experience rebound abnormalities in laboratory tests and/or relapses, and some of them have recurrences after an apparently full recovery. Histological documentation is useful to confirm the diagnosis. The effect of methotrexate and TNFα antagonists is modest at best. A few patients have responded to tocilizumab, which suppresses IL-6, a key cytokine in GCA. Life expectancy in GCA patients is similar to that in same-age controls except for a slight excess in vascular mortality shortly after the diagnosis.     

Post-dural puncture headache in the parturient

Post-dural puncture headache (PDPH) is a common and debilitating complication of central neuraxial blockade in the parturient. The obstetric population is at particular risk with up to 80% of women developing symptoms after accidental dural puncture (ADP) during labour epidural insertion. PDPH typically develops 24–48 hours post puncture and is classically described as an occipito-frontal headache with postural features. Diagnosis and assessment should include consideration of other potential causes of post-partum headache. Initial treatment of PDPH includes adequate hydration and analgesics. Epidural blood patch (EBP) remains the gold standard treatment. It is more successful if performed over 24–48 hours after the development of symptoms. Complete and permanent relief of symptoms following a single EBP occurs in up to one third of cases where headache follows ADP with an epidural needle. Complete or partial relief may be seen in 50–80% overall. Higher success rates are achieved following a second EBP. There is now UK national guidance on the treatment of post dural puncture headache published by the Obstetric Anaesthetists Association (OAA).     

Temporal arteritis in the young

Temporal arteritis in the form of giant cell arteritis (GCA) is common in the elderly but is extremely rare in patients less than 50 years of age. We describe two male patients: one who presented at the age of 31 years with painful, nodular swellings of both temporal arteries and whose temporal artery biopsy demonstrated a non-giant cell panarteritis with mixed inflammatory cell infiltrate typical of juvenile temporal arteritis (JTA); another one, aged 40 years, who presented with headache and cerebral angiography consistent with an intracranial vasculitis and whose temporal artery biopsy confirmed an authentic multinucleated GCA. The first patient spontaneously improved after biopsy and the second patient has responded well to corticosteroid therapy. These two cases exemplify well two distinct but extremely rare forms of temporal arteritis in young patients. A 3rd subset is that associated with a systemic vasculitis. Few cases of JTA have been reported and, to our knowledge, we describe in this report one of the only cases of GCA with central nervous system involvement in the young.     

Effects of long-term treatment with mizoribine in patients with proliferative lupus nephritis

AIM: Mizoribine (MZR) is a purine antimetabolic immunosuppressant agent that has few little severe adverse events. We studied whether maintenance therapy with MZR and prednisolone (PSL) in severe proliferative lupus nephritis patients could improve immunity, reduce proteinuria, prevent renal relapse, and reduce steroid dose. METHOD: Long-term maintenance therapy with MZR and PSL was evaluated in ten patients with biopsy-proven proliferative lupus nephritis. Patients with severe lupus nephritis, who had proteinuria of 0.5 g or more even after treatments with plasma exchange and/or pulse methyl prednisolone, were recruited. MZR at an average dose of 140 +/- 10 (100 - 200) mg was administered two to three times/day in combination with PSL. The average period for the MZR maintenance therapy was 89.7 +/- 5.5 (70 - 126) months. Urine protein excretion, serum hemolytic complement activity (CH50), C3, serum creatinine, general and biochemical blood examinations, anti-ds-DNA antibody were collected at each monthly medical examination. RESULTS: All patients were females, mean age 43.0 +/- 3.3 years. A significant decrease in proteinuria was noted two years after the combination therapy (p = 0.0016). Five patients experienced lupus nephritis relapse. Patients who did not experience relapses had their MZR combination therapy initiated earlier (p = 0.037) when compared with the patients who experienced relapses. Serum creatinine levels remained unchanged in all patients throughout treatment and follow-up, even during renal relapses. Levels of C3 and CH50 normalized as proteinuria decreased. None of the patients developed serious side effects during MZR treatment. A significant steroid-sparing effect was observed three years after initiating MZR (p = 0.0025). CONCLUSION: From our long-term observation, maintenance therapy with low-dose PSL combined with MZR can eliminate proteinuria and have steroid-sparing effect. Early initiation of the therapy can protect against renal relapses among severe proliferative lupus nephritis patients without serious side effects.     

Medical treatment strategies to reduce perioperative morbidity and mortality after carotid surgery

There is a paucity of high-quality evidence regarding what constitutes “optimal medical therapy” for the purposes of reducing morbidity/mortality after carotid endarterectomy (CEA). All patients should be prescribed antiplatelet therapy. Low-dose aspirin (75 to 325 mg) should be continued throughout the perioperative period and there is no evidence that higher doses confer additional benefit. There is emerging evidence that early implementation of dual antiplatelet therapy in recently symptomatic patients (aspirin 75 mg plus clopidogrel 75 mg) can reduce recurrent cerebral events before CEA and that dual antiplatelet therapy will significantly reduce stroke due to early postoperative carotid thrombosis. Evidence suggests that dual antiplatelet therapy is not associated with a significant increase in bleeding complications, although it is essential to aggressively treat post-CEA hypertension. Antiplatelet therapy should be withheld for 24 hours after completion of thrombolysis. Statins should be started preoperatively; the rationale being that they will reduce perioperative myocardial infarction and stroke (especially in symptomatic patients), as well as reduce recurrent cerebral events before CEA. Heparin reversal using protamine is becoming increasingly common and there is no evidence that this significantly increases perioperative thromboembolic stroke, but it does seem to reduce the prevalence of neck hematomas, which can be associated with an increased risk of stroke/death after re-exploration. Post-CEA hypertension is especially common in recently symptomatic patients undergoing surgery within the first 7 to 14 days after onset of symptoms. Untreated, it is associated with high rates of intracerebral hemorrhage, stroke due to the hyperperfusion syndrome, and major cardiac events. Each unit should have written guidance for treating this condition promptly. This is especially important when CEA is performed in the first few days after onset of symptoms and, especially, when CEA is performed soon after thrombolysis.     

Posttraumatic headache

Opinion statement Posttraumatic headache (PTH) is divided into acute and chronic groups whose management and prognosis are clearly different. Although IHS criteria stipulate that PTH should have an onset within 2 weeks of the trauma, it has been observed that a headache linked to the trauma can start later. PTH can be clinically divided into the following groups: migraine-like headache, tension-type-like headache, cluster-like headache, cervicogenic-like headache, and others. Based on these clinical distinctions, therapy can be administered accordingly. However, the distinction is relative and numerous clinical features may be common to all. There seems to be a weak inverse relationship between the severity of the head trauma and the occurrence of a PTH, especially chronic. A holistic approach is not only useful but it is necessary for a therapeutic success. Early and aggressive treatment and empathy are essential to the patient’s improvement. Prompt recognition and treatment of laceration, peripheral nociceptive sources such as cervical joint displacement, vascular factors, may diminish chronicity. Neuromodulation of pain with prophylactic agents is recommended early. Although it is less necessary for the acute PTH, it will be crucial for the chronic form and should be initiated no later than 2 months cut-off time between acute and chronic PTH. Recognition and treatment of psychiatric factors such as depression and anxiety will lessen the risk of chronicity. Analgesic rebound-withdrawal headache commonly is seen in chronic PTH. This must be corrected rapidly because it can protract the headache and render other inappropriate therapeutic measures inefficient.