Table of contents:

1. What is Rheumatology? What is a Rheumatologist?
2. Osteoarthritis
3. Osteoarthritis of the Knee
4. Alkaptonuria and Ochronosis
5. PMR/TA

PMR/TA
History: The term PMR was first used by Stuart Barber in 1957 to describe 12 aching elderly people with elevated ESR who had no other explanation such as infection, inflammatory disorder or neoplasm to explain the elevated ESR. J. Paulley and J. Hughes in 1960 linked PMR to TA.

Epidemiology: PMR patients are typically all over 50 years old and most are 60-80 years old. At the Mayo Clinic a study spanning thirty years of patients and some 378 cases showed the incidence was 58.7 /100,000 cases. The mean age at onset was 72.8 years old and sixty six percent were women. In Denmark the incidence is 68.3/ 100,000 cases, in Norway 113/ 100,000 cases and in Southern Spain it is 13.5/ 100,000. HLA-DR4 has been associated with PMR and HLA-DRB1*04 if the PMR is associated with TA. IL-6 promoter polymorphism at position 174 modulates phenotypic expression of PMR and TNF promoter biallelic polymorphism modulated expression of PMR but not TA. There is an increased prevalence of PMR in Caucasians compared to Blacks, Hispanics, Asians and Native Americans. The Caucasian American population in the northeast has a higher prevalence than whites in the southeast. In summary there are two epidemiologic trends. The first trend is a higher rate of PMR if Northern versus Southern countries. The second trend is the increasing incidence which at the Mayo Clinic over 46 years has increased 2.6% every five years. Clinical: The clinical presentation is one of stiffness and pain with an insidious onset. Stiffness and pain is mostly proximal and symmetrical although unilateral pain occurs occasionally at the onset. The shoulder is the number one site of involvement and as with all joints involved may have limited mobility.
Constitutional symptoms. These include fatigue, malaise, low grade fever which occasionally goes to 102 and can present rarely as an FUO. You can also get night sweats, anorexia and weight loss which will mimic malignancy.
Neuropsychiatric: Depression but also dementia, acute disorientation and/or amnesia with no focal neurologic deficits.
Myalgia: Proximal, chronic and symmetrical frequently over shoulders and hips. Stiffness is worse in the morning and sufferers may need to be lifted out of bed. Aching is worse with exertion and muscles may be tender to palpation. Over time you can get disuse atrophy and contractures. It is very hard to check strength.
Arthralgias: May have an abrupt onset of pain and even night pain. The pain is poorly localized but often found in the hips and shoulders in which bicipital tendinitis and subacromial and subdeltoid bursitis in association with glenohumeral joint effusion may be identified. Radionuclide bone scans, MRI and ultrasound studies have all suggested synovitis with effusion may occur in shoulders and hips. You may see a moderate to large (30-150ml.) knee effusion in two studies involving 31 and 38 percent of PMR patients. Also seen may be swelling of the hands, wrists (occasionally with carpal tunnel syndrome), knees and sternoclavicular joints. Peripheral arthritis may occur in conjunction with pitting edema of the hands either initially or later in the course.
TA: Up to 35% of PMR patients develop TA.

Laboratory studies: Westergren ESR if over 50 and frequently greater than the age of the patient. CRP is positive and may go up earlier than ESR. IL6 is a pro inflammatory cytokine that is important in the induction of the acute phase reaction. The interleukin 6 level may be the most accurate to follow as it follows disease activity better than ESR and predicts relapse better than the ESR. The ESR may be normal in as many as 20% of PMR patients. Studies of the normal ESR in PMR population show them to be younger, more often male, have fewer systemic and laboratory abnormalities and respond better to low dose corticosteroids than the population with PMR and high ESR. The ESR should normalize 7-10days after starting corticosteroids.
Normocytic, normochromic anemia in 50%
Hepatic alkaline phosphatase is elevated in about a third of cases and occasionally the liver scan is abnormal. Alkaline phosphatase should normalize after starting steroids in 3 weeks, if it does not one should consider bone scans and further workup.
Rheumatoid factor, ANA, CK, Aldolase, LDH and SGOT are all normal.
Synovial fluid is 1000-8000 largely lymphocytes, followed by polymorphonuclear leukocytes. Studies for cultures and crystals in synovial fluid are negative.
Muscle biopsy shows normal or non diagnostic changes or type II B fiber atrophy.
Temporal artery biopsy is only necessary if there are signs and/or symptoms of temporal arteritis or if treatment of PMR with corticosteroids fails after on month.
Differential Diagnosis: Central to this is an elderly person with no muscle weakness, normal CK and normal T4 but has arthralgias and myalgias and an elevated ESR with a dramatic response to low dose steroids. The differential should include:
Rheumatoid/Psoriatic arthritis- The joint involvement is more distal and the rheumatoid factor or HLA-B27 may be positive.
Systemic/Drug induced Lupus- The serologies will be positive.
RS3PE-Predominantly older men with only distal symptoms, almost all edema and pain.
Fibromyalgia
Myositis including inflammatory, malignant, drug induced especially steroids and statins, inclusion body myositis
Thyroid abnormalities- hyperthyroidism gives you weakness and elevated T4 but normal CK and ESR. Hypothyroidism will give you pain, no weakness, normal ESR, elevated CK and low T4.
Paget’s disease
Neoplasm- The association of PMR and malignancy is unclear in the literature. Several neoplasms have been reporter as mimicking PMR and these include renal cell carcinoma, sarcoma, multiple myeloma, lymphoma, leukemia and the non neoplastic amyloid. One should think of neoplasm if the presentation is PMR-like but the ESR if less than 40 or greater than 100, if there is a poor response to corticosteroids, if the age is less than 50 and or if the clinical manifestations are limited or asymmetric.
Infection- Consider in any elderly person especially if they have systemic symptoms and/or diabetes.
Depression- May mimic any disorder in the elderly but ESR is normal.
Temporal Arteritis- depending on the study may occur in 15-78% (15-20% in North America, 50% in Scandinavia) and in a few percent of cases of TA occurring with PMR you may not elicit signs or symptoms of TA but only find a positive biopsy. PET scans have shown increased uptake in the aorta of PMR patients suggesting subclinical arteritis.
Diagnosis: There is no absolute test for PMR. Westergren ESR has been the standard but it can be negative in up to 15-20% of cases. C reactive protein goes up earlier than ESR but like ESR is nonspecific. IL6 may become a valuable adjunct once laboratories develop more familiarity with it. PET scans with 18F-glucose have been shown to light up in sixty percent of large thoracic arteries in PMR with ischemic symptoms. This may be a subclass of TA or evidence they are the same disease.Etiology: The etiology is unknown however any putative agent must explain the predilection for the elderly, for Caucasians and for HLA-DR4. IL1 and TNF are causes of inflammation in PMR. IL10 may play an antiinflammatory role and its production at high levels results in a favorable outcome in PMR with shorter courses of steroids and lower levels of IL1 and TNF. There is also a debate on whether a subclinical myopathy exists which some investigators have described as a mitochondrial myopathy.

Treatment: Prednisone at 10-15mg split tid should elicit a dramatic response in 48-72 hours. Rarely 20mg or more is needed or the person may respond to Methylprednisolone or Dexamethasone preferentially. Shoulder pain has improved with injections of 40mg of Triamcinolone Acetate into the subacromial bursa.
ESR usually returns to normal in 7-10 days. If a dramatic response does not occur, stop the steroid and reconsider the differential. If a dramatic response does occur consolidate to a single morning dose in one month and then slowly taper at about one mg/month. Increase only for an increase in symptoms and ESR not just a change in the ESR. If the patient has recurrence or new symptoms but not an increase in the ESR look for soft tissue conditions or osteoarthritis. Remember osteoporosis will worsen on steroids and must be monitored and a minimum of Ca 1500mg/day and Vitamin D 800 IU/day must be given with the corticosteroids. Also monitor glucose and beware K fluctuations and muscle cramps. Nonsteroidal antiinflammatory agents may improve mild disease in 15-20% of cases according to the Mayo Clinic and also may suppress soft tissue syndromes. Steroid sparing drugs may be necessary to help with a taper. Steroid sparing drugs studied in PMR include Methotrexate, Azathioprine, Dapsone, Cyclosporine and Trimethoprim/sulfamethoxazole.
A current debate in treatment is over the fact that corticosteroids do not shorten the duration of the disease nor do they necessarily reduce all signs of disease activity, they primarily suppress symptoms and ESR. Von Willebrand factor which elevates when there is vascular endothelial dysfunction does not normalize in PMR patients of corticosteroids. Only 8-10% of cases taper off corticosteroids in the first year and more aggressive cases may require steroids indefinitely.Prognosis: Tends to resolve in 24-50 months. Isolated cases have gone on for years and relapse rate is 20% occurring over months to a year or two after cessation of therapy. One recent theory is that there are two populations of PMR patients, one with mild disease that responds within two years to treatment and one with more severe disease that has the need for treatment for much more than two years. The latter group is characterized has having a higher mean age at onset, being more often female, having a higher ESR at diagnosis and requiring more corticosteroids throughout the course. Overall there is no increased mortality for PMR.

Temporal Arteritis
AKA: cranial arteritis or giant cell arteritis or granulomatous arteritis or Horton’s headache. The Chapel Hill consensus criteria meetings for vasculitis classified temporal arteritis as a large vessel vasculitis along with Takayasu’s arteritis. However TA may be also defined as a chronic vasculitis of large and medium sized arteries characterized by symptomatic vessel inflammation predominantly affecting the aorta and its external branches especially the superficial temporal artery.
History: First described in the English literature by Jonathan Hutchinson in London in 1890. The case involved an elderly servant named Rumbold who worked for the Earl of Dun Donald. The man had inflamed temporal arteries and it hurt for him to wear his hat. Some reports suggest that Hutchinson thought Rumbold wore a too tight hat and that resulted in inflamed temporal arteries.
However a report by Bayard Horton and colleagues in 1932 recognized the granulomatous arteritis and included the first live temporal artery biopsies.
Epidemiology: Temporal arteritis with or without PMR is more common in women with a trend in the last decade toward even higher occurrence in females and lower occurrence in males. The peak age at onset is between 63 and 73 years old. However several new studies suggest incidence is much higher in patients in there eighties compared to fifties. In the population over 50 years old the annual incidence is 24.1/100000 in Olmstead, Minnesota and is on the rise. TA is increased in whites of Northern European descent (27.1/100,000) but prevalence in blacks (0.4/100,000), Hispanics (11.5/100,000) and Asians (Japan <0.1/100,000) is not as low as once thought. A North-South gradient exists worldwide, Scandinavia has the highest occurrence reported in persons over 50 years old and ranging from 15-35/100,000. There are some studies have shown seasonal variation, urban versus rural differences and even cyclic changes over the decades but none that have been consistently repeated.
Etiology: The etiology is unknown although speculation has included virus, bacteria, neoplasm and immune or allergic disorder. Any etiologic agent must explain the age distribution, the distribution of artery involvement which appears to correlate with elastin content and the chronic granulomatous changes (macrophages and CD4+ T lymphocytes of the Th1 type with 25% activated T cells) in the blood vessels. Some have speculated that the presence in the lesions of antigen presenting cells, CD4+ lymphocytes, Th1 differentiation of infiltrates all suggest a delayed type hypersensitivity reaction to an antigen in the vessel wall. Sixty percent or more are HLA-DR4 positive if they have PMR/TA but not TA alone and also an association exists with the HLA-DRB1*04 allele. The risk of ominous visual complications is also higher if DRB1*04 is present. Case control studies suggest a higher risk of TA in cigarette smokers and those with previous peripheral vascular disease. TA prevalence is lower in Japan and they also have less visual loss and jaw claudication and PMR. This may be partially explained by differences in HLA-DRB1 and in IL1 clusters and in TNF polymorphism. Japan also has much higher prevalence of the other large vessel vasculitis Takayasu’s arteritis.Clinical:
Any vessel anywhere in the body can be involved and the most common antecedent is PMR 40% and concurrent onset of PMR and TA is 20%. Presentation with cranial symptoms and signs such as headache, scalp tenderness, jaw and tongue claudication is also 20%. Four clinical subtypes have been identified and these include first cranial TA with eye, face and CNS ischemia, second large vessel TA with subclavian, axillary and aortic arch syndromes, third TA with systemics inflammation and non stenosing vasculitis and fourth isolated PMR with subclinical arteritis in the aortic arch vessels.

Headache: The headache is the most frequent symptom (44-98%) and also frequently the initial symptom and always beginning early. However headaches may rarely occur at one year and also may start early but then stop even though the disease remains active. It is described as dull, extracranial, boring and burning. Headaches may be episodic and lancinating pains that are worse at night. The headache can sometimes be localized over scalp arteries. Classically it is a temporal headache and the temporal arteries may be swollen or pulseless or more often just tender to touch. Patients with occipital artery involvement may find that combing their hair is painful and they have pain when laying their head on a pillow. Scalp tenderness occurs in 20-95% of cases and may on occasion result in necrosis.
Jaw Claudication: Jaw claudication was thought to be pathognomonic but has a differential which includes amyloid and a rare form of atherosclerosis affecting the external carotid artery. One Mayo Clinic study found with biopsy proven TA 54% had jaw claudication but if the TA biopsy turned out to be negative the only 3% had a history of jaw claudication. Neither fever nor headache nor scalp tenderness or even visual loss showed this type of difference. If the maxillary artery is involved with TA then claudication occurs in the jaw with facial pressure when singing and chewing and the patient becomes reluctant to eat. Trismus has also been described with reduction in the jaw opening. If lingual artery is involved then it is in the tongue which develops claudication, may blanch and very rarely will develop gangrene. Sometimes you may get pharyngeal pain. Claudication may occur in the extremities too.
Pain in the ear canal, pinna or parotid: May be secondary to posterior auricular artery involvement.
Temporal artery pain: may be secondary to temporal artery involvement.
Ocular: The most common ocular manifestation is ischemic optic neuropathy of which anterior ischemic optic neuropathy is more common than retrobulbar ischemic neuropathy. Amaurosis fugax may be a pre ischemic manifestation of optic neuropathy and forty percent go on to develop AION and 15% develop central retinal problems. Ocular manifestation occurs in 20-50% of patients and in patients who will ultimately develop eye problems it is present initially in 60%. Transient blurring of vision and/or loss of vision may occur but you can also occasionally see ptosis or double vision. There is almost always a prodromal period prior to visual loss and when loss occurs in one eye you have one to two weeks before the second eye is involved. Headache is the most common presenting symptom and it usually is present but forgotten having occurred before the ocular symptoms even when they present with ocular manifestations. PMR is the earliest finding in 30%. Visual loss is often irreversible unless treatment is initiated within 2-3 hours of onset. The retina is supplied by the central retinal artery which is the terminal branch of the ophthalmic artery. Also derived from the ophthalmic artery are the posterior ciliary arteries which supply the optic nerve and the muscular branches which supply the extraocular muscles. Involvement of the posterior ciliary arteries results in anterior ischemic optic neuritis, the most common ocular lesion. Retinal exam may be normal or there may be slight pallor of the optic disc with a few cotton wool patches and small hemorrhages. Involvement of the muscular branches of the posterior ciliary arteries results is ischemia of the extraocular muscles and in diplopia which occurs in 5%. Occlusion of the central retinal artery or its branches occurs in fewer than `10% of patients with eye involvement and therefore retinal changes such as exudates or hemorrhages are infrequent. Funduscopic examination will often be normal or the exam will show only mild edema of the nerve head several days after the onset of symptoms. Optic atrophy is a late finding.
Amaurosis fugax may be a pre ischemic optic neuropathy and occurs in about 10% of patients with TA. Forty percent go on to AION and 15% go on to central retinal involvement. Permanent visual loss will develop in 80% if no treatment at all if given.
Unilateral or incomplete blindness occurs in about 30-40% of patients and if untreated may progress to complete blindness over a period of several days.
Bilateral blindness occurs in 25% of patients with TA and is often preceded by amaurosis fugax or partial blindness.
Diplopia secondary to ischemic damage to almost every portion of the ocular motor system with paresis of the extraocular muscles occurs in about 5% of TA.
Visual hallucination has also been described in TA.
In one recent report of patients with TA presenting with ocular problems more than 20% had no systemic symptoms or laboratory abnormalities to the limit of the testing.Artery syndromes- these depend on the artery involved with abdominal pain from the mesenteric artery, extremity claudication with the iliac artery, stroke with the internal carotid or vertebral artery, angina with the coronary arteries, hypertension with the renal arteries etc.
Aortic arch and thoracic aorta: look for bruits over the carotid, axillary or brachial arteries. Checking blood pressure over both arms may also show asymmetric changes earlier than bruits. The differential diagnosis has to include atherosclerotic vascular disease. Both vasculitis and atherosclerosis can also result in CAD. Claudication can occur and the upper extremity is a common site of involvement. Arteriography will show long segments of smooth arterial stenosis and/or sudden cutoffs. Occasionally you may see aortic dissection at any level.
Abdominal aorta: can get symptoms secondary to aortic aneurysm and intestinal infarction.
Raynaud’s phenomenon has been described. Renal involvement is rare. Leg claudication has occurred. Please note that steroids should not be used for presumptive large vessel vasculitis in the elderly unless there is proven vasculitis somewhere since atherosclerosis is so common.
Constitutional symptoms and neuropsychiatric symptoms: identical to PMR with fatigue, malaise, fever (50%), anorexia, weight loss, stiffness, muscle and joint pain, depression, confusion, dementia etc. FUO has TA accounting for 2% but if you look at FUO in patients over 65 years old the percentage goes to 16% and two thirds have rigors and drenching night sweats but normal WBC prior to starting prednisone. If you look at age over 65 and fever and ESR over 100mm/hr the percentage is even higher.
Miscellaneous: A 2003 report of audio vestibular manifestations of TA found about 90% had vestibular dysfunction or hearing impairment at presentation. The audio vestibular findings are far more common in TA than pure PMR. Peripheral neuropathy, vertigo, angina pectoris/CHF, hemiparesis, and brainstem strokes have all been anecdotally described. Also hearing loss, microscopic hematuria and a recent report of elevated levels of plasma homocysteine before and after steroid therapy so that Folic acid is indicated.
PMR: In TA 41-63 percent may present with PMR. PMR may occur before during of after TA.

Diagnosis: Temporal artery biopsy: Should always be done as early as possible although inflammation in the artery will still be present after two weeks of steroid therapy if carefully looked for, but within seven days is ideal. Biopsy when unilateral should be done on the contralateral side if the initial biopsy is negative but the clinical findings are compelling. Temporal artery biopsy should be done only in the right clinical setting and if negative you should be prepared to stop steroids. However you can occasionally not have temporal artery involvement especially in the aortic arch syndromes where 42% have had negative temporal artery biopsies. Temporal artery biopsies will remain positive for 2-8 weeks depending on the completeness of the pathology search. Skip lesions are common. A large section of artery must be taken and biopsy should be bilateral if any question exists. Bilateral temporal artery biopsies add three percent to diagnostic yield although some studies are up to 15%. Occlude the artery before biopsy. Review vessel histology carefully with pathologist. The role of MRA, color duplex ultrasonography, PET scan and Gallium to isolate area to biopsy is still controversial. To date high resolution color coded sonography has shown the most potential although plain ultrasound does not work.
Laboratory Studies: You find elevated ESR (Westergren) whose result in mm/hr is greater than the patients stated age and frequently above 100. CRP is positive and is frequently very high (>10mg/dl) and may be very helpful when the ESR is low as with hereditary spherocytosis, white blood cells are slightly elevated and platelets are normal or slightly elevated. An ESR of less than 40 was associated with fewer systemic and visual symptoms in TA patients when compared to TA patients with higher ESR but the latter group had more headaches and PMR. Von Willebrand factor is often elevated in TA but is unfortunately neither sensitive nor specific. Normochromic, normocytic anemia with the Hg. averaging 11.4 is the norm and thrombocytosis may occur. Albumin is decrease and alpha two globulins and fibrinogen are increased. Only rarely is there a slight increase in immunoglobulins and one third have elevated liver tests including hepatic alkaline phosphatase, SGOT and PT. Liver biopsy may only show a fatty liver. Urinalysis is normal but occasional reports of casts that may be granular, tubular and/or RBC the latter seen with renal artery arteritis.
Serologies are negative, complement levels are normal, cryoglobulins and monoclonal antibodies are absent. However recent studies suggest IgG anticardiolipin antibodies may have a role and may predict outcome. IL6 may be the ideal way to follow TA in the future. CD8 T lymphocytes are found in lower than expected numbers and circulating soluble IL2 receptor levels are increased as are certain circulating adhesion molecules along with the IL6.
Synovial fluid has a WBC 1000-8000 with 40% polys, normal complement and synovial biopsy showing lymphocytic infiltrate.
Radiography in the form of temporal artery arteriography has no value.
Arteriography of the aorta may be useful. If arteriography reveals vasculitis you may see slowly tapering stenotic lesions in contrast to the cobblestone pattern of arteriosclerotic disease. Unfortunately elderly patients may have both.
PET scanning with fluoro 18 deoxy glucose focusing of the large thoracic arteries including the aorta, subclavian and carotid is specific but not sensitive for the arteritis and therefore not helpful for diagnosis of arteritis in the superficial temporal artery. MRA has been anecdotally helpful. 67 Gallium citrate which binds to transferrin receptors on activated macrophages either using scintigraphy or quantitative single photon emission CT may be very helpful but requires special expertise. Color duplex ultrasonography looking for the dark halo of vessel edema has shown the ability to light up unrecognized vasculitis or show involved segments of arteries but it is neither sensitive nor specific. Pathology of the artery: A positive temporal artery biopsy is diagnostic but a negative biopsy does not exclude the diagnosis as 10-15% may have false negative biopsies. The avoidance of false negative biopsies requires large segments of temporal artery to be biopsied. The rate of positive biopsy increases with the size of the biopsy specimen and is due to skip lesions. Recommendations are for over 2 centimeters to be biopsied and some reports recommend 3-6 centimeters. Pathologists will slice the artery at 1-2mm intervals and will vary the orientation of the slice to maximize results. Serial cross sectioning of the artery also increases the yield of positive biopsies. Bilateral biopsies may increase the yield by 1-5%.
The artery may show either granulomatous inflammation around the media near the internal elastic lamina with mononuclear cell, giant cells and fragmentation of the internal elastic lamina or an inflammatory infiltrate predominantly of mononuclear cells, usually involving the entire vessel wall (a panarteritis with no fibrinoid necrosis) or around internal and external elastic lamina or adventitia. Any vessel in the body could be involved. Congo red staining should always be done on the artery to rule out amyloid.
Fragmentation of the internal elastic lamina is a consistent feature of aging too and therefore not diagnostic in and of itself.

Giant cells may be spotted in 50-66% of cases and are multinucleated and Langerhans giant cells found especially in the internal elastic lamina
Intimal proliferation is often marked but nonspecific therefore not enough to diagnose TA alone.
When TA involves larger vessels the lesions are identical to Takayasu’s disease.
Thrombosis of vessels may occur especially in the acute lesions.
Diffuse arterial infiltrates alone may be seen in up to 40% of cases in some studies.
Healed temporal arteritis due to steroids only means the inflammatory infiltrate is gone you should still see intimal fibrosis, medial scarring and eccentric destruction of the internal elastic lamina.
IL1 and IL6 are principal mediators of vessel wall inflammation. Clonal expansion of CD4+ T cells produces gamma interferon which stimulates macrophages to release cytokines which include nitric oxide and matrix metalloproteinase. The latter stimulates smooth muscle cells to migrate toward the lumen where they will encounter platelet derived growth factor and vascular endothelial growth factor which stimulate intimal proliferation and neo angiogenesis.

Differential:

Arteriosclerotic vascular disease- can be confusing both with initial diagnosis and relapse
Takayasu’s arteritis: tends not to involve temporal artery, females predominate and the age is much lower 20-50 yo v. 60-80 yo. Takayasu’s does not have PMR

Systemic necrotizing vasculitis: occasionally involves temporal arteries but has fibrinoid necrosis and possibly neutrophil inflammation which is different. Also has kidney, peripheral nervous system and skin involvement which is rare with TA.

Amyloidosis, sarcoidosis, Wegener’s granulomatosis and SBE all have anecdotal reports of mimicking TA. Treatment: The treatment depends on the presentation. Steroids are usually started immediately, before biopsy if the presentation merits it and the risks of steroids such as diabetes control and CHF are not an issue. Acute eye manifestations with threatened vision require immediate admission to the hospital and administration of 1mg/kg Medrol at a minimum and frequently either a gram of Solu-Medrol IV or 10mg of Dexamethasone IV. The vision must be monitored for visual acuity every four hours. Non acute presentations would be treated with 1mg/kg of Medrol or equivalent in split doses with consolidation in one month. The same precautions for osteoporosis and diabetes as are taken in PMR should be taken here. Response to initial treatment (as far as constitutional symptoms and PMR) should occur in 36-72 hours and the ESR should normalize in 7-10 days and headache, scalp tenderness, jaw and tongue claudication may take a little longer. Steroid sparing medications used include Methotrexate (one recent study did not show benefit as a steroid sparing drug), Imuran, Cytoxan, Dapsone, Cyclosporin and Plaquenil. Methotrexate in three controlled studies has had disparate results while the results of Dapsone have been poor. Cytoxan has had good outcomes for steroid sparing but the drug side effects convey high risk. Trimethoprim/sulfamethoxazole has helped anecdotally in steroid resistant cases. Future treatments may well involve the TNF inhibitors such as Infliximab and Etanercept which already have shown benefit with anecdotal reports and controlled studies have started. Every other day steroids work neither for TA of PMR and intravenous is not necessarily better than oral if you give equivalent potency.

Prognosis: Relapse if it occurs will occur usually in the first 18months after stopping therapy. Relapse rates are variously reported between 32 and 65%. With relapse the ESR and CRP may be normal. However sometimes the ESR is normal but the CRP is not and the IL6 level may be the most sensitive for relapse diagnosis. Ultimately in both PMR and TA about 14% develop RA. Because steroids are required for 2-3 years or more by one year complications of the steroids can exceed complications of the disease. Risk of death from TA increases three times normal in the first four months of the disease and patients die of vascular complications such as stroke and heart attack. The prognosis of TA returns to the normal age matched level after four months except for a 17 times increase in thoracic aortic aneurysm and aortic dissection. Therefore any new aortic insufficiency murmur should be considered a medical emergency. Finally fifteen percent of all TA patients may suffer permanent cranial ischemic complication that occur prior to or just after treatment and usually entail visual loss. This visual loss is from delayed diagnosis and treatment and is an area that improvement can occur.