Behcet's syndrome : vasculitis of unknown cause affecting characteristically venules. There is a striking geographical distribution, it being most common in Turkey, Iran and Japan.

The prevalence per is in Japan and in Turkey. There is a link to the HLA-B51 allele (a split antigen of B5), with a relative risk of 5-10.

CLINICAL FEATURES there is a wide range of clinical features. The disease is characterized by unpredictable exacerbations. There is no definite investigation & the diagnosis is made depending on clinical criteria:

*recurrent oral ulcerations – minor aphthous, major aphthous or herpitiform ulceration at least 3 times in a 12 month period.

Plus 2 of the fallowing : 1-recurrent genital ulceration(60-80%) 2- eye lesions : anterior uveitis, posterior uveitis, cells in vitreous on slit-lamp examination, retinal vasculitis. The involvement is usually bilateral.

3- skin lesions: erythema nodosum, pseudofolliculitis, papulopustular lesions, acne form nodules, migratory thrombophlebitis& vasculitis 4- positive pathergy test: involves intradermal skin pricking with a needle, a pustule develops within 48 hours.

Other manifestations include a self-limiting peripheral mono-or oligoarthritis affecting knee, ankle, wrist and elbows; gastrointestinal symptoms of diarrhea, abdominal pain and anorexia; pulmonary and renal lesions; brainstem syndrome; organic confusional state and meningo-encephalitis.

All the common manifestations are self-limiting except ocular attacks. Repeated attacks of uveitis can cause blindness. The pathology is highly specific to Behcet's disease. Recurrent thrombosis can occur. Renal involvement is rare.

TREATMENT Steroid(topical), immunosuppressants& cyclosporine are used for chronic uveitis& the rare neurological complications, colchicine for skin disease& arthralgia, thalidomide mg/day for 28 days for oral & genital ulceration, but this drug is highly teratogenic(phocomelia)& neurotoxic. Systemic manifestations require systemic steroids& immunosuppressive drugs.

Inadequate and delayed mineralization of osteoid in mature compact and spongy bone Major deficit is in Vitamin D, which is required for Ca++ uptake in intestines Decreased Ca++ stimulates PTH, which does increase Ca++, but also increases phosphate excretion by kidney When phosphate levels too low, mineralization cannot occur Osteomalacia (Adult Rickets)

4 categories of osteomalacia &rickets can be identified based on the underlying cause: 1- deficiency of v.D or defects in v.D metabolism. 2- hypophosphatemia. 3- drug induced inhibition of bone mineralization. 4- defects in pyrophosphate metabolism.

Etiology More prevalent in extreme preemies, elderly, those following strict macrobiotic vegetarian diets and persons on anticonvulsant Rx Pancreatic insufficiency Hepatobiliary diseases Lack of bile salts decreases absorption of Vit D Malabsorption syndromes Hyperthyroidism Rare in US due to fortification of foods Common in GB and Middle Eastern Countries

Clinical Presentation Generalized body aches /LBP as well as hip pain Lower extremity pain & deformity Physical examination Scoliosis / kyphosis of spine Deformities of weight bearing bones Muscle weakness leading to classic waddling gait Generalized Malaise

Patients with chronic renal failure cannot synthesize the active metabolite of v.D(1,25(OH)2D3) due to renal damage& this causes secondary hyperparathyroidism & in some cases osteomalacia.

Diagnosis Serum Ca++ – ↓ or Normal Serum inorganic Phosphate ↑ > 5.5 Vitamin D ↓ BUN & creatinine ↑ Alkaline Phosphatase & PTH ↑ Bone bx to determine aluminum levels X-Rays Demineralization Pseudofractures Bowing of long bones

Radiological examination is of limited value unless in advanced cases where focal radiolucent area ; pseudofracture or looser's zones are seen in ribs, pelvis& long bones. Radiological osteopenia &crush vertebral fracture may cause confusion with osteoporosis.

Diagnosis of osteomalacia is confirmed with bone biopsy which shows pathognomonic increased thickness of osteoid seams.

Clinical Management Correcting serum Ca++ & phosphorous Chelating bone aluminum if needed Suppressing hyperthyroidism Supplement with Vitamin D Administer Ca++ carbonate to ↓ hyperphosphatemia Renal dialysis/transplant for renal osteodystrophy Correction of associated intestinal disorders

The response will be rapid clinically& radiologically. After 3-4 months, the treatment can be stopped or the dose of v.D is reduced to the maintenance. Patients with chronic renal failure require 1-alpha (OH)D or 1,25(OH)2D to bypass the metabolic defect in 1- alpha hydroxylation of 25(OH)D.

Screening of serum Ca& alkaline phosphatase is needed during treatment to avoid hyperCa. Alkaline phosphatase returns to normal after treatment.

Excess of bone destruction & unorganized bone formation and repair. The 2 nd most common bone disorder in the U.S. The etiology is unknown Usually affects the axial skeleton, vertebrae and skull, although the pelvis, tibia, femur are the other common sites of disease. Most persons are asymptomatic & diagnosis is incidental. Paget’s Disease (Osteitis Deformans)

Vascularity is increased in affected portions of the skeleton. Lesions may occur in one or more bones, does not spread from bone to bone. Deformities & bony enlargement often occur. Bowing of the limbs & spinal curvature in persons with advanced disease. Bone pain- is the most common symptom. Is usually worse with ambulation or activity but may also occur at rest. Involved bones may feel spongy & warm because of increased vascularity. Skull pain is usually accompanied with headache, warmth, tenderness & enlargement of the head.

Pathologic fractures- because of the increased vascularity of the involved bone-bleeding is a potential danger. Alkaline phosphatase levels- markedly elevated as the result of osteoblast activity. Serum calcium are normal except with generalized disease or immobilization. Gout and hyperuricemia may develop as a result of increased bone activity, which causes an increase in nucleic acid catabolism.

Radiograph reveals radiolucent areas in the bone, typical of increased bone resorption. Deformities & fractures may also be present. Goals of the treatment- to relieve pain & prevent fracture & deformities. Pharmacologic agents are used to suppress osteoclastic activity. Bisphosphonates & calcitonin are effective agents to decrease bone pain & bone warmth & also relieve neural decompression, joint pain & lytic lesions. Use of analgesics & NSAIDs. Assistive devices, including cane, walker.

Deformities may be corrected by surgical intervention (osteotomy). ORIF may be necessary for fractures. The patient may benefit from a PT referral. Local application of ice or heat may help alleviate pain. A regular exercise should be maintained; walking is best. Avoid extended periods of immobility to avoid hypercalcemia. A nutritionally adequate diet is recommended. Assistance in learning to use canes or other ambulatory aids. The Arthritis Foundation & Paget Foundation are useful resources for patients & their families.

Osteoporosis Characterized by low bone mass and structural deterioration Normal homeostatic bone remodeling is altered – the rate of bone resorption is greater than the rate of bone formation.

Eight times more common in women than men for several reasons 1. Lower calcium intake than men 2. Less bone mass because of smaller frame 3. Bone resorption begins earlier and accelerates after menopause 4. Pregnancy and breastfeeding deplete woman’s skeletal reserve of calcium 5. Longevity increases likelihood of osteoporosis; women live longer than men

Etiology Risk factors (non-modifiable) Female gender Increasing age Family history White or Asian ethnicity Small stature Early menopause

Risk factors (cont’d) Excess alcohol intake Cigarette smoking Anorexia Oophorectomy Sedentary lifestyle Insufficient calcium intake Low testosterone levels (hypogonadism in men)

Etiology and Pathophysiology Peak bone mass is achieved before age 20 Bone loss after midlife is inevitable but rate of loss is variable Bone resorption exceeds bone deposition Bones become weakened and prone to fracture, loss of height, and kyphosis.

Etiology and Pathophysiology Diseases associated with osteoporosis Intestinal malabsorption Kidney disease Rheumatoid arthritis Hyperthyroidism Chronic alcoholism Cirrhosis of the liver Hypergonadism Diabetes mellitus

Osteoporosis Diagnostic Studies Clinical Manifestations Known as silent disease Diagnosis Bone Mineral Density (BMD) Dual-energy x-ray absorptiometry (DEXA) History and physical Quantitative ultrasound

Treatment and Nursing Care Diet Therapy Weight bearing Exercises Decrease Risk Factors Quit smoking and decrease consumption of alcohol

Drug Treatment of Osteoporosis Estrogen Replacement Therapy Calcium & Vitamin D supplements Calcitonin Biphosphonates (Fosamax, Didronel, Actonel, Boniva, Aredia, Bonefos, Skelid) Selective Estrogen receptor modulator – Evista Teriparatide (Forteo) Portion of parathyroid hormone First drug to stimulate new bone formation

Hormone Replacement Therapy – Estrogen Controversy over use. Should discuss with health care provider Calcium There are a variety of calcium supplements available (See Table 64-16, p. 1689). They should be taken with _______ _ to aid in absorption. Also if taking large doses i.e mg. / day – take in divided doses of 500mg BID for better absorption

Calcitonin If calcitonin inhibits bone resorption by opposing the effects of parathyroid hormone, how does that affect serum calcium levels? What is needed to counter that effect?

*parathyroid hormone: the main action is bone formation. The hormone should be given in an intermittent dosing to alleviate the risk of bone resorption in cases of sustained hyperparathyroidism. The available drug is teriparatide which is given as single S.C. daily dose.