Halux Limitus / Rigidus The big Toe rules proper footmechanics

Your big toe, Hallux or great toe is a very important structure of the proper function of the lower extremity. Most of the people they don’t pay any attention to their toe unless it’s too ugly or hairy or too long and of course when it’s injured.

Hallux Limitus is described as a restriction IN the range of motion (ROM) of the big toe motion. Such motions are Plantar Flexion that means moving toe towards the floor and Dorsi Flexion meaning movement of the toe upwards.

Hallux Limitus can be extremely painfull or can be present with no pain at all. Even if there is no pain this condition should be concerned because its very important for the biomechanics of the Toe/ Ankle/Knee/ Hip and low back. Can create some compensations of the body that can be surely unpleasant for the patient.

Hallux Limitus can be caused from various circumstances. In athletes, trauma is the most common reason. The degree of trauma can vary from minor repetitive stress to severe trauma. Over pronation is a common cause of repetitive stress that is not felt until is too late.

Improper body mechanics and dysfunctional movement patterns, can lead to compensations which may cause over pronation of the foot during gait. Wearing short shoe or constrictive can also cause Hallux Limitus. In general, if the big toe is forced to hyperextension can result to the Hallux Rigidus condition. If the hyperextension is a minor one, then you can realize there is problem until the condition sets –in.

Under normal conditions, with each step, your foot must expand to absorb and distribute with loading of your bodyweight. Your arch or more specifically, your longitudinal arch takes the brunt of these forces. Your foot and arch then lengthens at which time, your big toe has to extend to tighten up the tendons and ligaments and plantar fascia of your foot to both support these forces and utilize potential energy so you have a little ‘’spring’’ in your step… literally. This is often referred to as the ‘’windlass’’ effect.

When working correctly, your foot should roll onto your big toe after the ‘’windlass’’ effect and you should push off of this very rigid yet ‘’springy’’ ‘’strut’’. If you have Hallux Limitus, this does not occur, the big toe does not extend enough and you will end up pushing off of your 2^nd or third toe while walking, running, jumping etc.

This is not only an inefficient way to go about moving around in life, it can cause you to compensate in your ankle, knee, hip and even low back to keep things moving smoothly. Over time, this may result in injuries to these structures (due to overload) and, through a series of complex compensatory patterns, transfer the foreces into your upper back, neck and jaw leading to a myriad of problems.

One such a problem is the problem that is still within the foot structure is the development of a bunion or Hallux Valgus. As the foot/leg complex tries desperately to roll off of the big toes (which won’t let this happen because it can’t extend correctly), the rest of your foot will roll in putting forces on the metatarsal joint of the big toes which causes it to be pushed laterally. Over time, the joint (as seen in the picture) will become deformed and the big toe will angle awkwardly towards your other toes.

No matter what the cause of Hallux Limitus is , repetitive hyperextension and/or compression to the joints of the big toe will eventually cause inflammation resulting in early breakdown of the cartilage protecting the ends of the two bones. Without treatment the degenerative process will continue, forming cartilaginous spurs. With progression these cartilage structures can calcify into bony spurs. The end-stage of this disorder is a condition known as Hallux Rigidus, where the joint literallu fuse and no motion is left within it. Even with this as a possibility, much of the dysfunction that results from hallux limitus is not due to the injury to the joints of the big toe, but the compensation that takes place elsewhere in the body.

Hallux Limitus is easily detected by a well-trained doctor and can usually be treated conservatively with self-mobilization, pronation, controlled shoes, possibly orthotics, manipulation and Kinesiotape and Granston Technique. The first noticeable change with Hallux Limitus is loss of ability to dorsiflex (or extend) your big toe. Normal ROM is about 65 degrees. If you notice limitations or pain in the big toe joint with dorsiflexion, or your shoes are wearing unevenly, or have asymmetrical calluses on your feet, it may be time to visit your clinician.

REHABILITATION INTERVENTIONS OFTEN USED IN RHEUMATIC DISEASES

Many rehabilitation interventions have been recommended for patients with rheumatic disease. This section presents an overview of indications and contraindications of the most common rehabilitation interventions used in patients with rheumatic disease.
Education and self-management
Education and self-management are widely regarded as being fundamental to the comprehensive management of rheumatic diseases, in particular rheumatoid arthritis. Patient associations in North America have been instrumental in developing and making available multiple resources. Self-management training can be provided by other patients or by healthcare providers. The programs provided by peers have been extensively
studied and shown to improve pain, function, selfefficacy, and satisfaction.86 They can reduce visits to healthcare providers and associated costs. Programs provided by care providers have been less studied but appear to provide similar benefits.
The programs with the best results focus on active learning in peer groups, with an emphasis on problem solving and increasing self-efficacy. They also include information on the nature and prognosis of arthritis; efficacy and side effects of arthritis medications; and exercise, pacing, and other rehabilitation interventions.


Exercise, rest, and energy conservation
Exercise and exercise-based rehabilitation programs are interventions well supported in controlled trials. Exercise improves range of motion, strength, and functional activities in osteoarthritis, rheumatoid arthritis, and extraarticular rheumatism.
 The exercise program must be individualized according to the disease activity, accumulated joint damage,
and the patient's goals and interests.
 In general terms, high-impact exercises such as jumping, basketball, etc. should be avoided in patients
with significant rheumatic disease. Medium-impact exercises such as walking, jogging, bicycling, and swimming are appropriate, unless there is severe joint inflammation.
Severely inflamed joints should only be subjected to gentle mobilization and stretching within the available range of movement.
Strategies for joint protection, energy conservation, and pacing are frequently recommended by occupational therapists. Often, patients develop their own strategies for energy conservation. However, there is limited evidence of efficacy in this regard.


Physical modalities
Heat, cold, and other physical modalities have been used to treat rheumatic conditions for centuries.Most of these modalities have been accepted by tradition, and only recently have been subjected to controlled trials,also Local heat can decrease pain, at least temporarily, and can be easily applied by patients or family members if precautions to avoid burns are taken.There is a theoretic possibility that local heat can
increase the inflammatory response and possibly increase joint damage, but this has not been supported empirically.The usual contraindications to local heat application. Local heat can be applied by conduction (heat pads and water bottles), radiation (incandescent lamps and infrared lamps), or immersion (hot water, paraffin baths, and mud baths) .There is no solid evidence that one method is preferable to another, and the choice depends on availability and the body part to be treated. For example, paraffin baths are ideally
suited to apply heat to the rheumatic hand.Cold and contrast baths (heat alternating with cold) have been described, but there are no adequate studies to support their utility in rheumatic disease. In the absence of conclusive scientific evidence, the patient's comfort and preferences should take precedence.
Ultrasound and diathermy mostly function as conversion methods of applying heat to the deeper tissues, although there might be additional mechanisms at play.Recent studies have reported the use of shock waves to treat tendonitis and fasciitis, but rigorous randomized trials have questioned their efficacy.
Interferential currents have little application for treating joint disease, but functional electrical stimulation is sometimes used to prevent muscle atrophy during episodes of intense disease activity.
Transcutaneous electrical nerve stimulation might relieve the pain of rheumatic disease,and

animal studies suggest it can also decrease joint swelling.
Electromagnetic fields have established efficacy in accelerating fracture healing,' and available trials suggest some benefit in knee osteoarthritis. Low-power laser has been poorly studied but might provide short-term relief of pain and stiffness.


Manual and mechanical therapies
Manual therapies have been extensively used to treat regional musculoskeletal pain and extraarticular rheumatism.They are seldom prescribed in rheumatoid arthritis or severe osteoarthritis, because they are typically considered to be alternative or integrative therapies. Nevertheless, many patients make use of them outside the medical establishment.
Traction is sometimes recommended for patients with back or neck pain, but randomized controlled trials have not demonstrated benefit.
Acupuncture could be classified as a mechanical therapy, in that it produces mechanical stimulation by the needle, but diverse theories exist about its mechanism of action.Controlled studies are rare, but preliminary evidence suggests benefits in osteoarthritis of the knee.

THORASIC OUTLET SYNDROME (TOS)

Thoracic outlet syndrome is actually a collection of syndromes brought about by abnormal compression of the neurovascular bundle by bony, ligamentous or muscular obstacles between the cervical spine and the lower border of the axilla.

What does that mean?

First of all a syndrome is defined as a group of signs and symptoms that collectively characterize or indicate a particular disease or abnormal condition.

• The neurovascular bundle which can suffer compression consists of the brachial plexus plus the C8 and Tl nerve roots and the subclavian artery and vein.
• The brachial plexus is the network of motor and sensory nerves which innervate the arm, the hand, and the region of the shoulder girdle.
• The vascular component of the bundle, the subclavian artery and veintransport blood to and from the arm, the hand, the shoulder girdle and the regions of the neck and head.

The bony, ligamentous, and muscular obstacles all define the cervicoaxillary canal or the thoracic outlet and its course from the base of the neck to the axilla or arm pit. Look at the scheme of this region and it all becomes more easily understood. 

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What are the signs and symptoms of thoracic outlet syndrome?

It is important to understand that presenting with the symptoms listed below in no way indicates a definitive diagnosis for thoracic outlet syndrome. Professionals understand the importance of coupling diagnostic testing skills with the patient's report of what hurts and what doesn't seem to be working properly. Don't self diagnose! Neurologic and vascular symptoms can be indicative of more serious conditions.

Vascular symptoms include:	Neurologic symptoms include:
Swelling or puffiness in the arm or hand Bluish discoloration of the hand Feeling of heaviness in the arm or hand Pulsating lump above the clavicle Deep, boring toothache-like pain in the neck and shoulder region which seems to increase at night Easily fatigued arms and hands Superficial vein distention in the hand	Parasthesia along the inside forearm and the palm (C8, T1 dermatome) Muscle weakness and atrophy of the gripping muscles (long finger flexors) and small muscles of the hand (thenar and intrinsics) Difficulty with fine motor tasks of the hand Cramps of the muscles on the inner forearm (long finger flexors) Pain in the arm and hand Tingling and numbness in the neck, shoulder region, arm and hand

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What causes the neurovascular compression?

Compression occurs when the size and shape of the thoracic outlet is altered. The outlet can be altered by exercise, trauma, pregnancy, a congenital anomaly, an exostosis, postural weakness or changes.

Below is a list of the component syndromes which comprise thoracic outlet syndrome along with a brief description of each. Refer to the scheme for questions about the gross anatomy of the region.

Anterior scalene tightness

Compression of the interscalene space between the anterior and middle scalene muscles-probably from nerve root irritation, spondylosis or facet joint inflammation leading to muscle spasm.

Costoclavicular approximation

Compression in the space between the clavicle, the first rib and the muscular and ligamentous structures in the area-probably from postural deficiencies or carrying heavy objects.

Pectoralis minor tightness

Compression beneath the tendon of the pectoralis minor under the coracoid process-may result from repetitive movements of the arms above the head (shoulder elevation and hyperabduction).

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What sort of activities can cause these compression syndromes?

Thoracic outlet syndrome has been described as occurring in a diverse population. It is most often the result of poor or strenuous posture but can also result from trauma or constant muscle tension in the shoulder girdle.

Static postures such as those sustained by assembly line workers, cash register operators, students of, for example, those who do needle work often result in a drooping shoulder and forward head posture. This position of the shoulders and head is also indicative of poor upper body posture. Middle aged and elderly women who suffer from osteoporosis often display this type of posture as a result of increased thoracic spinal kyphosis.

Carrying heavy loads, briefcases and shoulder bags can also lead to neurovascular compression. Humans are not well adapted as beasts of burden and heavy loads hung form the shoulders and arms can stress the supporting structures of the shoulder girdle which is basically suspended by the clavicle and all of the component ligaments and muscles.

Occupations which require repetitive over head arm movements can also produce symptoms of compression . Electricians, painters and plasterers may develop hyperabduction syndrome. Compression of the neurovascular structures also occurs in athletes who repetitively hyperabduct their arms. Swimmers, volleyball players, tennis players and baseball pitchers may suffer compression of the neurovascular structures as well. However, compression of these structures may be caused by stretching or microtrauma (small tears in muscle tissue) to the muscles which support the scapula.

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Are there other causes of thoracic outlet syndrome?

Some people are born with an extra rib right above the first rib. Since this intersection of nerves, vessels, muscles, bones and ligaments is already quite involved one can imagine what the presence of an extra rib in the region might do. A fibrous band extends from this cervical rib to the first rib causing an extra bend in the lower part of the brachial plexus which may produce a compression in this region.

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How is thoracic outlet syndrome treated?

The first step to beginning any treatment begins with a trip to the doctor. Make a list of all of the symptoms which seem to be present even if the sensations are vague. Make a note of what activities and positions produce or alleviate the symptoms and the time of day when symptoms are worst. Also, note when the symptoms first appeared. This list is important and should also include any questions one may have.

Due to overlapping in terms of symptoms it is difficult to make a definitive diagnosis; this is why a list is so important. Certain diagnostic tests have been designed which are very useful for examination. These tests involve maneuvers of the arms and head and can help the practitioner by providing information as to the cause of the symptoms and help in designing an approach to treatment. These tests, accompanied by a thorough history help in ruling out other causes which may produce similar symptoms. These include Pancoast tumor, neurofibromas, cervical spondylosis, cervical disk herniation, carpal tunnel syndrome and cubital tunnel syndrome. Don't forget to ask your practitioner about these conditions as well.

Here are a few more commonly applied provocation tests used in the diagnosis of thoracic outlet syndrome. These tests may or may not momentarily reproduce symptoms but as was mentioned earlier are important in ruling out other causes which may produce similar symptoms.

EAST Test or "Hands-up" Test The patient brings their arms up as shown with elbows slightly behind the head. The patient then opens and closes their hands slowly for 3 minutes. A positive test is indicated by pain, heaviness or profound arm weakness or numbness and tingling of the hand.

Adson or Scalene Maneuver The examiner locates the radial pulse. The patient rotates their head toward the tested arm and lets the head tilt backwards (extends the neck) while the examiner extends the arm. A positive test is indicated by a disappearance of the pulse.

Costoclavicular Maneuver The examiner locates the radial pulse and draws the patient's shoulder down and back as the patient lifts their chest in an exaggerated "at attention" posture. A positive test is indicated by an absence of a pulse. This test is particularly effective in patients who complain of symptoms while wearing a back-pack or a heavy jacket.

Allen Test The examiner flexes the patient's elbow to 90 degrees while the shoulder is extended horizontally and rotated laterally. The patient is asked to turn their head away from the tested arm. The radial pulse is palpated and if it disappears as the patient's head is rotated the test is considered positive.

Provocative Elevation Test This test is used on patients who already present with symptoms. The patient sits and the examiner grasps the patient's arms as shown. The patient is passive as the shoulders are elevated forward and into full elevation. The position is held for 30 seconds or more. This activity is evidenced by increased pulse, skin color change (more pink) and increased hand temperature. Neurological signs go from numbness to pins and needles or tingling as well as some pain as blood flow to the nerve returns. Similar to what is felt after an arm "falls asleep" and circulation returns.

Once a diagnosis is decided, every effort is made for a conservative treatment approach. That means it won't hurt. Should symptoms persist over 3 or 4 months or if there is intractable pain, vascular loss or neuralgic loss then surgery should be considered. Surgery is consistent in relieving pain but muscle weakness and atrophy do not usually improve significantly.

Conservative treatment usually includes local heat and a program which address postural retraining, shoulder strengthening and stretching exercises. The practitioner will create a treatment program specific to the presenting symptoms. Below are a few self-stretching exercises. All of these exercises should be performed slowly and carefully. Each position is assumed smoothly to the point where a stretch is felt intensely but with no pain. There should be no bouncing in any of these positions. Hold the stretch for 30 seconds and then gently and slowly release it. Wait 10 seconds and repeat the stretch 3-5 times. If the stretches increase the symptoms do not continue.

Stretching the back of the neck Using the arm which is on the side of the tightness assume the position which is demonstrated, the head turning away from the pain (left image). The hand behind the head helps stabilize the head position. Take a deep breath, exhale slowly while bending the knees keeping the elbow where it is against the wall. Another method for stretching the back of the neck can be accomplished by sitting down in a sturdy chair (right image). Turn the head away from the tight side, look down until a slight stretch is felt. Reach down with the hand on the tight side and hold onto the chair. With the other hand pull the head forward, gently.

Stretching the chest Sit in a sturdy backed chair with the hands clasped behind the back of the head as demonstrated (see image, top left). Bring the elbows back as far as possible during a slow, deep breath in. While exhaling slowly bring the elbows together letting the head bend forward slightly (bottom left). Another method for stretching this area is to stand facing a corner or a doorway with the arms in a "U" or a "V" against the wall or door posts (see right image). With the knees bent lean slightly forward from the ankles.

Stretching the side of the neck Sit in a sturdy chair. Hold the underside with the arm of the tight side. Pull the head back making a double chin. Bend the head away from the tight side and turn the head toward the tight side. It won't go very far. Lean away from the arm holding onto the chair and reach with the opposite arm to the top of the head and gently pull to increase the stretch.

Stretching the shoulder and the chest There are three exercises for this region:
	Sit in a sturdy chair next to a table with the arm placed as demonstrated, palm down. Slide the arm forward while bending at the waist as far as is possible without pain. Eventually the head should be level with the side of the table.

Stand with back to the table and grasp the edge with the fingers facing forward. Bend the knees and lower the body allowing the elbows to bend. Let the knees do the work.
Sit on a firm and sturdy surface with the hand of the tight side grasping the edge. Lean away slowly.

Mobilization of the first rib Use a large bath towel and grasp it at opposite corners. sling it across the shoulder of tightness and bring both ends across to the opposite hip or waist. With the arm on that side pull gently downward then release slowly.

These stretches are not cures. They may help in alleviating some of the symptoms of thoracic outlet syndrome but as with any exercise program one should always consult a physician before beginning particularly when symptoms persist for any length of time.

http://www.nismat.org

Polymyalgia Rheumatica and Giant Cell Arteritis

Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are two related, immune-mediated, inflammatory conditions that occur in the elderly. PMR coexists in 40% of patients with GCA. Similarly, 10% of PMR patients develop GCA at some point during their disease course. The relation between PMR and GCA is further demonstrated by their preference for similar patient populations, linkage to the same HLA haplotypes, similar cytokine patterns in temporal artery biopsies, and similarities in anatomic involvement on PET imaging.^1-3 PMR and GCA represent two extremes of a disease spectrum.

Polymyalgia rheumatica

Definition

Bruce is credited with the first description in 1888 of PMR, which he described as “senile rheumatic gout.”⁴ However, Barber coined the term polymyalgia rheumatica in 1957, and it has become the universally accepted name for this condition.⁵

PMR is characterized by proximal, symmetrical musculoskeletal pain and stiffness. Symptoms of systemic inflammation are also common. A dramatic response to low-dose corticosteroids can be a valuable diagnostic tool in patients for whom the diagnosis is uncertain. The lack of response to prednisone raises the possibility of a paraneoplastic process manifesting with proximal pain and stiffness. In patients who have a dramatic response to treatment there is still a need for caution because some patients (~11%) with an initial PMR-like presentation evolve into a phenotype that is more that of rheumatoid arthritis and, less often, other systemic rheumatic illnesses.⁶

Epidemiology

PMR has a predilection for patients older than 50 years. The mean age at onset is 73 years, and women are affected more often than men. Its annual incidence in Olmstead County, Minnesota, a population with mostly Scandinavian heritage, is 59 per 100,000. The annual incidence of the disease increases with age.⁷ Whites of northern European descent have a higher incidence of disease than people of African American or Latin American descent.^8,9

Pathophysiology

Much has been learned about PMR and GCA, but their cause remains unknown. Their cause is likely multifactorial, resulting in the interplay of age, environment, and genetic susceptibility. The suggestion that PMR may be a forme fruste of GCA was first advanced in the 1950s and 1960s.⁵ The pathophysiology for both diseases is similar, with abnormalities of cellular immunity leading to vessel and systemic inflammation. Sixteen percent to at least 20% or more of PMR patients demonstrate arteritis on histologic examination, requiring the diagnosis to be changed to GCA.¹⁰ Cytokines such as interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α are important in the development of inflammation in GCA.¹¹Messenger RNA (mRNA) for interferon-gamma (IFN-γ) and IFN-γ protein, a product of Th1 lymphocytes, is found in the arterial wall of GCA patients. This suggests that IFN-γ may be a necessary element in the development of vasculitis. The classic histologic features of GCA, which include inflammatory cells involving the adventitia of a muscular artery and migrating toward the media and intima, consist of Th1 cells, dendritic cells, and macrophages.⁹

Signs and Symptoms

Most patients describe subacute onset of symptoms that remain persistent over time. Seventy percent to 95% of patients report symmetrical shoulder girdle pain and stiffness. Fifty percent to 70% report neck and pelvic girdle pain. Concurrent pain in the upper arms and thighs is common and is usually worse in the morning. Shoulder and leg discomfort can lead to difficulty dressing, hair grooming, and rising from a chair. One third of patients have flulike symptoms described as fever, malaise, anorexia, or weight loss.¹²

Physical examination findings may reveal pain that limits active range of motion in the shoulders and hips. Passive range of motion should be normal. Despite subjective symptoms of muscle weakness, muscle strength testing should be normal unless it is affected by examination discomfort or by another condition.¹² Approximately 50% of patients have been said to present with distal extremity abnormalities including swelling of the knees, wrists, or metacarpophalangeal joints. Other reported findings include soft-tissue swelling; pitting edema of the hands, ankles, and feet; and median nerve compression. However, these findings are typical of inflammatory joint disease and not PMR. The examiner should direct the evaluation along other lines in attempting to define another diagnosis. Frank synovitis of the hands or feet should suggest rheumatoid arthritis or another inflammatory arthropathy. Thus, further laboratory and imaging may be needed to differentiate the two. (See the chapter “Rheumatoid Arthritis”).

Diagnosis

The diagnosis of PMR is based primarily on clinical features. Elevated acute phase reactants provide secondary support for the diagnosis. The erythrocyte sedimentation rate (ESR) is greater than 40 mm/hr in 90% of cases. Other laboratory findings include an elevated C-reactive protein (CRP), normocytic normochromic anemia, thrombocytosis, and elevated alkaline phosphatase. Elevation of muscle enzymes, such as creatine kinase and aldolase, is not a feature of PMR and should prompt consideration of an alternative diagnosis.

In 1979, Bird and colleagues proposed diagnostic criteria for PMR (Table 1). Patients who fulfilled any three criteria or had one criterion along with vasculitis on a temporal artery biopsy were considered to have PMR.¹³ In 1984, Healy proposed that patients older than 50 years, seronegative for rheumatoid factor, and any three clinical features (neck, shoulder, or pelvic girdle pain, morning stiffness, elevated ESR, or rapid response to low-dose steroids) have PMR.¹⁴ Although these criteria should serve as guidelines for the diagnosis of PMR, most authorities agree that no single feature is necessary to diagnose it in all cases. The features noted in these criteria are common enough that if patients present without these symptoms or have a suboptimal response to corticosteroids, the diagnosis should be reconsidered. Conditions that can mimic PMR include malignancies, chronic infections, drug reactions, and other rheumatic conditions such as seronegative rheumatoid arthritis or polymyositis.⁶

Table 1: Often-Cited Diagnostic Criteria for Polymyalgia Rheumatica

Authors and Year Proposed	Proposed Criteria	Requirement for Making Diagnosis
Bird et al. (1979)	Age ≥65 yr Bilateral shoulder pain and stiffness Acute or subacute onset (<2 wk) ESR >40 mm/hr Depression and/or weight loss Bilateral tenderness in upper arm muscles Morning stiffness >1 hr	Any three of these criteria, or any one plus positive temporal artery biopsy
Jones and Hazelman (1981)	ESR >30 mm/hr or CRP >6 mg/L Shoulder and pelvic girdle pain Exclusion of rheumatoid arthritis or other inflammatory arthropathy, myopathy, malignancy Morning stiffness >1 hr Rapid response to corticosteroids	All criteria must be met
Chuang et al. (1982)	Age ≥50 ESR >40 mm/hr >1 mo bilateral aching and stiffness of at least two of the following areas: Neck or torso, shoulders or proximal arms, hips or proximal thighs Exclusion of other causes	All criteria must be met
Healey (1984)	>1 mo of neck, shoulder, or pelvic girdle pain (any two areas) Morning stiffness >1 hr Elevated ESR (≤40 mm/hr) Exclusion of other diagnoses Rapid response to daily, low-dose steroid therapy (e.g., prednisolone ≤20 mg)	All criteria must be met

CRP, C-reactive protein; ESR, erythrocyte sedimentation rate.
© 2004 The Cleveland Clinic Foundation.

Treatment

The first successful use of corticosteroids in patients with PMR was reported by Kersley in 1951.⁵ Since that time, it has remained the cornerstone of therapy for PMR. Prednisone or prednisolone is the most commonly used corticosteroids. Starting doses range from 15 to 20 mg per day. A dramatic response to therapy with near-total relief of symptoms should occur within 1 to 5 days. Lack of a dramatic response to corticosteroids should prompt physicians to reconsider the diagnosis. A gradual decline of the acute phase reactants should be expected but should never be the sole gauge of therapy. After an adequate response to corticosteroids has been achieved, the initial dose should be maintained for 1 month before beginning a slow taper to the lowest effective dose. One to 2 years of treatment with corticosteroids should be expected, and a few patients require low-dose prednisone for several years.¹⁵

Disease flares during the corticosteroid taper are common and often require temporary increases in therapy. Disease flares can occur in the presence of normal acute-phase reactants. Increases in acute phase reactants mandate an evaluation to be sure that comorbid conditions are not responsible for such changes. Isolated increases in acute-phase reactants should lead to more careful monitoring and not to reflexive increases in corticosteroids doses.¹⁶

Corticosteroids are the cornerstone of therapy, but they are not without side effects. Most patients have at least one relapse as corticosteroids are tapered, and adverse events occur in almost every patient. The role of immunosuppressive agents other than corticosteroids in PMR is controversial. Methotrexate has been studied in two randomized, double-blind, controlled trials. Van der Veen and colleagues reported that patients randomized to take oral methotrexate (10 mg/week) had the same number of relapses and received the same total cumulative prednisone dose compared with patients who received placebo.¹⁷ Caporali and colleagues reported that patients randomized to oral methotrexate (10 mg/week) for 48 weeks had fewer relapses and required lower cumulative prednisone doses than patients who took placebo.¹⁸ However, further review of the patients who received methotrexate revealed that they had the same number of relapses while they were taking prednisone as did patients who received placebo. Furthermore, the number of corticosteroid-related adverse events was equal in both treatment groups and the total cumulative prednisone dose reduction achieved by taking methotrexate in place of placebo equaled only about 1 mg/day.¹⁹

TNF-α, a cytokine produced by macrophages and T-lymphocytes, appears to play a significant role in the inflammatory process of PMR and GCA. In one pilot study, 3 mg/kg of intravenous infliximab was administered as adjunctive therapy to patients on corticosteroids. This therapy allowed 12 months of remission in three out of four patients treated with the drug.²⁰ These results were not seen in a recent double-blind, randomized, placebo-controlled study by the same author. Patients who received 3 mg/kg of infliximab at the same dosing intervals as used for rheumatoid arthritis over 22 weeks experienced the same number of weeks in remission as those who received placebo. No difference was seen in the duration of corticosteroid therapy or in the total number of patients who were able to discontinue corticosteroids between the groups.²¹

Outcomes

Adequate treatment with corticosteroids allows most patients to remain symptom free. Patients who have PMR need continued follow-up to monitor for drug-related toxicities and for possible progression to GCA. The development of a new headache or visual changes should prompt immediate medical evaluation and institution of higher doses of corticosteroids. Bilateral upper- and lower-extremity blood pressures should be obtained periodically. Differences between contralateral extremity pressures of 10 mm Hg or more should be considered abnormal. Bruits over carotid, subclavian, or femoral arteries may be due to either atheromatous disease or GCA and require further evaluation by vascular imaging.

Giant cell arteritis

Definition

GCA is a vasculitis characterized by granulomatous inflammation of medium-sized and large arteries. Inflammation is seen more commonly in the extracranial branches of the carotid arteries and other primary branch vessels of the aortic arch. Less often, internal branches of the carotid are affected, most notably the ophthalmic and posterior ciliary arteries; stenosis or occlusion of these arteries can cause loss of vision. At least one out of five patients develop large-vessel inflammation that can lead to branch vessel (e.g., most often subclavian) stenosis and less often aneurysmal dilation of the aorta (especially aortic root) or branch vessels.²² GCA is the most common vasculitis in whites older than 50 years. It has a predilection for people of northern European heritage. Women are affected at least twice as often as men.⁹

Prevalence

In the United States, GCA affects about 18 of 100,000 people older than 50 years. The epidemiologic characteristics of GCA are similar to those of PMR. The incidence of GCA is much higher in the northern latitudes, with a mean age at onset of 74 years. GCA and PMR might represent opposite ends of a disease spectrum, with many patients presenting features of both diseases. Approximately 40% of GCA patients have concurrent features of PMR at some point during their disease course.²³

Pathophysiology

Figure 1: Click to Enlarge

The cause of GCA is unknown, but vessel inflammation is cell mediated and not autoantibody induced. Dendritic cells, macrophages, and Th1-lymphocytes enter the vessel wall via the vasa vasorum and spread through the arterial adventitia.²⁴ A small fraction of activated T lymphocytes in the artery wall become clonally expanded. The cause for the clonal expansion is unknown but may be from a yet-unidentified neoantigen present in the arterial wall.²⁵ A broad range of proinflammatory cytokines, growth factors, and metalloproteinases are associated with inflammatory cell migration throughout the arterial media and intima. This panarterial inflammation leads to arterial damage, intimal proliferation, and ultimately luminal narrowing (Fig. 1). The luminal narrowing is responsible for ischemic events (loss of vision, stroke, and claudication). Understanding how these cytokines participate in inflammation will lead to better-targeted therapies in both GCA and PMR.²⁶

Signs and Symptoms

Headache is the most common symptom in GCA and occurs in 63% to 87% of patients. Systemic symptoms including fever, weight loss, and myalgias occur in 50% of patients.²⁷ Other symptoms include scalp pain, jaw pain while chewing, and arm or leg claudication. Vision loss, the most dreaded complication of GCA, occurs in more than 30% of patients.²⁸Anterior ischemic optic neuropathy is the most common cause of blindness. Twenty-seven percent of patients develop either an aortic aneurysm or large artery stenosis at some point during their disease course. Six percent of patients who develop an aortic aneurysm present with symptoms consistent with a dissection of the aneurysm.²² Extremity claudication occurs when aortic branch vessels, such as the subclavian artery, become critically narrow. Stroke and vision loss can occur without any preceding symptoms; however, patients can present with insidious nonspecific symptoms before the diagnosis of GCA is made. Forty percent of patients present with symptoms not considered classic for GCA. These symptoms can include cough, throat pain, or tongue pain.

A thorough physical examination may reveal a prominent, tender temporal artery. Evaluation of the artery may reveal a decreased pulse and a nodular appearance. Asymmetrical extremity blood pressures or pulses, bruits over subclavian or carotid arteries, or a murmur of aortic insufficiency suggests aortic or primary aortic branch involvement.

Diagnosis

Similar to PMR, no serologic test is diagnostic for GCA. Diagnosis is based on clinical symptoms in the presence of abnormal acute-phase reactants. More than 90% of patients have an elevated ESR. An elevated CRP, alkaline phosphatase, and platelets are not uncommon. Temporal artery biopsy is considered the standard diagnostic test for GCA. The sensitivity of biopsy, in series from medical practitioners, in detecting GCA is about 50%.²⁹ The yield of biopsy is a function of pretest probability, which might explain why some ophthalmology and other series, in which visual abnormalities were common, have yields as high as 80%.³⁰ Biopsy of the contralateral temporal artery adds very little to the sensitivity of the test.³¹

Figure 2: Click to Enlarge

Imaging of the vessel lumen with arteriography or magnetic resonance arteriography (MRA) may reveal aortic or arterial branches with stenoses or aneurysms (Fig. 2). The subclavian arteries, carotid arteries, and ascending aorta are the most commonly affected areas. Other arterial branches, such as the mesenteric and renal arteries, can also be affected. Vascular PET imaging with ¹⁸F-fluorodeoxyglucose may reveal vessel uptake in GCA as well as PMR. It is a more sensitive marker for disease than biopsy, but its diagnostic specificity is still in the process of being defined.³²

Treatment

Corticosteroids are the drug of choice for the treatment of GCA. They quickly reduce symptoms and decrease risk of visual complications from 60% to 14%.³³ Therapy with corticosteroids should start when GCA is first suspected. Waiting to start corticosteroids until after a temporal artery biopsy could result in irreversible loss of vision.

The optimal initial dose of prednisone is unclear, but most authorities agree that the initial dose should be between 40 and 60 mg/day. Doses of at least 60 mg are preferred when presenting features include ophthalmic or neurologic complications. Some authorities advocate intravenous methylprednisolone at doses of 1000 mg a day for 3 to 5 days in patients presenting with blindness.^33-35 The initial oral dose of corticosteroids should continue for 1 month before taper is considered. Many tapering schedules exist but few have been studied in clinical trials. One general rule is to taper by 10% to 20% every 2 weeks.⁹ Treatment duration is different for each patient. Long-term therapy is required in most patients. It is not unusual for corticosteroid therapy to extend beyond 4 years.^36-38

The efficacy of methotrexate in Wegener's granulomatosis and Takayasu's arteritis has led to its use in three randomized, double-blind, placebo-controlled trials for GCA. Jover and colleagues reported that patients randomized to methotrexate doses of 10 mg/week had fewer relapses and lower cumulative steroid doses compared with those who received placebo. However, a difference in relapse rates was only noted after 1 year of disease. There was no advantage to methotrexate in the first year. In addition, patients who received methotrexate had the same number of steroid-related side effects as those who received placebo.³⁹ Hoffman and colleagues conducted the only multicenter, randomized, double-blind, placebo-controlled trial of methotrexate at doses of 15 mg each week. Their conclusions did not support the use of methotrexate as adjunctive therapy with corticosteroids. Patients who were randomized to receive methotrexate did not have reduced disease activity, cumulative corticosteroid doses, or corticosteroid-related toxicities.⁴⁰ Spiera and colleagues reported similar results.⁴¹ The use of adjunctive methotrexate as a steroid-sparing agent in patients with GCA remains a controversial issue.

Figure 3: Click to Enlarge

The finding of abundant TNF-α in GCA arteries (Fig. 3) has led investigators to study TNF-α inhibition as a potential disease modulator in GCA. Hoffman and colleagues reported results of a multicenter, randomized, double-blind, placebo-controlled trial of intravenous infliximab as adjunctive therapy to corticosteroids in patients with newly diagnosed GCA.⁴²The study was stopped at 22 weeks when infliximab was shown to not improve durability of remission or reduce cumulative steroid doses. The results of this study suggest that although TNF is found in abundance in affected vessels, it might not play a critical role in the pathogenesis of GCA. Other mediators might play more important roles in disease propagation.

Aspirin (ASA) is known to reduce the risks of ischemic stroke and myocardial infarction.^43,44 No prospective trial has ever been done to see if antiplatelet therapy reduces the risk of cranial ischemic complications in patients with GCA. A recent review of 175 GCA patients by Nesher and colleagues observed that patients who took low-dose ASA (100 mg/day) were five times less likely to present with visual complications or stroke.⁴⁵ A second report by Lee and colleagues showed similar results in patients on antiplatelet or anticoagulant therapy.⁴⁶ Sixteen percent of GCA patients taking ASA, warfarin, or clopidogrel developed an ischemic event compared with 48% of patients not on this therapy (P < 0.0005). Bleeding complications were not increased in the patients on antiplatelet or anticoagulant therapy. The authors concluded that adjunctive low-dose ASA should be considered in all patients with GCA who have no contraindications for its use.

Outcomes

Some studies have found that the overall mortality in patients with GCA is similar to that of age- and gender-matched controls. Other studies have noted an increase in mortality, particularly from cardiovascular events. There is agreement that patients with GCA are at higher risk of death from the complications of aortic aneurysms. Thoracic aneurysms are 17 times more likely to occur in GCA patients and can occur at any time during the disease course. Fifty percent of patients with aortic aneurysms experience dissection or rupture of their aneurysm.^22,47-49 Cost-benefit data are not available. Because the risks of aortic catastrophes are well documented, we recommend careful auscultation for aortic valve murmurs or bruits, which should be followed by MRA or CT angiography to determine the nature and seriousness of the aortic lesion. Size of the lesion, hemodynamic consequences, and change over time per sequential imaging determine the need for surgical interventions.

Nearly every patient treated with long-term corticosteroids develops complications related to therapy. Sixty percent develop severe adverse events such as corticosteroid-induced diabetes, avascular necrosis, glaucoma, or vertebral fractures.⁵⁰Corticosteroid-induced osteoporosis is a well-known complication of long-term steroid use. Medications such as calcium, vitamin D, and anti-resorptive agents should be considered in every patient who will receive corticosteroids for more than 3 months. Screening for osteoporosis with bone densitometry at the induction of corticosteroid therapy (and at regular intervals) is as important an intervention as prescribing steroids to prevent blindness.

Summary

• Clinicians should inquire about headache, jaw pain, and vision loss in all PMR patients at every clinic visit because 10% will develop GCA at some point during their disease course.
• Lack of a response to corticosteroids or the inability to taper below 20 mg/day should raise the possibility of a paraneoplastic process in patients with GCA.
• Isolated increases in acute phase reactants in GCA and PMR should never lead to reflexive increases in corticosteroids doses but lead to more careful monitoring for a disease flare.
• Aortic aneurysms occur in about one of five patients with GCA and should be periodically screened for in every patient.
• Corticosteroids remain the standard of care for the treatment of GCA and PMR.

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