Adhesive capsulitis of the shoulder is a common problem manifested by diffuse shoulder pain associated with a loss of motion in all directions and little or no evidence of intraarticular disease (4). The joint capsule is thickened and adherent to the humeral head. Arthroscopy reveals a marked reduction in the volume of the glenohumeral joint. Increased uptake of ^99mTc-methylene diphosphonate by the periarticular tissue has been demonstrated, suggesting the presence of inflammation (5). Bone demineralization follows. Although patients may recover spontaneously within 3 years, the syndrome may recur, and some patients with severe disease may become disabled (3).

The association of adhesive capsulitis and diabetes mellitus has been well documented. Bridgman (6) identified adhesive capsulitis in 11% of 800 diabetic patients as compared with an incidence of 2.5% in 600 control patients. Alternatively, abnormal glucose tolerance tests were seen in 28% of patients with adhesive capsulitis compared with 12% of age- and sex-matched controls attending a rheumatology clinic (6). Arkkila et al. (7) found an overall cumulative prevalence of shoulder capsulitis of 14% in patients with diabetes mellitus. The prevalence was 10% in patients with type 1 diabetes and 22% in patients with type 2 diabetes. Furthermore, adhesive capsulitis is associated with age in patients with type 1 and type 2 diabetes and with duration of diabetes in patients with type 1 diabetes only. Pal et al. (8) found adhesive capsulitis in 20.4% of patients with type 1 diabetes, in 18.3% of patients with type 2 diabetes, and in 5.3% of normal control subjects.

The treatment of patients is directed toward increasing the range of motion of the tightened joint. Early physical therapy, including exercises, heat, and ultrasound, may be helpful. Splinting may lead to further restriction of motion and is contraindicated. Treatment of pain during physical therapy is important. Treatment includes the use of nonsteroidal antiinflammatory drugs (NSAIDs) as both antiinflammatory agents and analgesics. In addition, opioids may occasionally be necessary. Although there are no long-term studies concerning the use of local glucocorticoid injections in this setting, intraarticular injections may occasionally be useful in decreasing pain and increasing motion. In our experience, full recovery of motion may take as long as 6 months. Rarely, patients may require manipulation of the shoulder while they are under
general anesthesia to increase the range of motion. In severe cases of adhesive capsulitis, the patient may not recover full motion and may become disabled.

Shoulder-hand syndrome (SHS) is characterized by adhesive capsulitis of the shoulder associated with pain, swelling, tenderness, dystrophic skin, and vasomotor instability in the hand. It is one of a family of disorders that includes reflex sympathetic dystrophy syndrome, major and minor causalgia, Sudeck atrophy, and algodystrophy. Doury et al. (9) described these syndromes as consisting of severe pain disproportionate to the findings of the physical examination in association with articular or periarticular swelling. Steinbrocker and Argyros (10,11) described three stages of this syndrome. During the first stage, which lasts 3 to 6 months, there is pain, tenderness, swelling, and vasomotor changes, including temperature and color changes in the affected hand. The second stage, which also may last 3 to 6 months, is characterized by trophic skin changes characterized by shiny skin with loss of normal wrinkling. The final stage is characterized by atrophy of skin and subcutaneous tissue, tendon contractures, and progressive osteopenia. Spontaneous improvement may occur, although without treatment the patient may lose function of the affected limb permanently.

Trauma is the most common condition predisposing to SHS, but diabetes; cerebrovascular disease; myocardial infarction; post-thoracotomy state; hyperthyroidism; hyperlipidemia; electrocution; medications, including barbiturates, isoniazid, ethionamide, and cycloserine; and previous exposure to radioiodine, have all been associated with the onset of this syndrome (3). In one study of 108 patients with SHS or related conditions, 7.4% had diabetes (9). The prevalence of diabetes actually may be greater in patients with this syndrome, since glucose tolerance tests were not performed in all cases.

Radiographic findings in SHS typically include a diffuse, patchy osteopenia. Measurements of bone mineral density demonstrate loss of up to one third of the bone mass. Three-phase bone scintigraphy reveals asymmetric uptake and increased blood flow and, in most cases, pooling in phases 1 and 2. The phase-3 images are characterized by increased uptake in the periarticular tissues. A small percentage of patients may show decreased uptake on bone scintigraphs.

Treatment of patients with SHS is most effective when begun early in the development of the syndrome. Analgesic medication and range-of-motion exercises should be prescribed. If these are ineffective, systemic glucocorticoid therapy or sympathetic blockade should be considered. In patients with diabetes, regional sympathetic-ganglion block with a long-acting anesthetic agent, performed by an anesthesiologist, is the preferred treatment method since the use of systemic glucocorticoids may cause difficulties in the maintenance of glucose control. Steinbrocker and Argyros (11) reviewed 146 patients with SHS and found some improvement in up to 80% treated with glucocorticoids or regional sympathetic blockade. Intraarticular steroids may also be used, but no controlled trials exist and experience with this technique is limited. Patients are candidates for surgical sympathectomy if the above approaches provide only temporary relief of symptoms. Recently, interest has increased in the use of α-adrenergic blockade and other vasoactive drugs in the treatment of SHS.

Diabetic hand syndrome (DHS), also termed cheiropathy, stiff-hand syndrome, diabetic stiff hand, diabetic contractures, or syndrome of limited joint mobility, was first described by Jung et al. (12) in adults with diabetes and by Grgic et al. (13) in a pediatric population with diabetes and short stature (see reference 14 for a comprehensive review of this syndrome). The syndrome has since been described in juveniles with type 1 diabetes and normal stature and in adults with type 1 or type 2 diabetes (15,16,17,18,19). The reported prevalence of DHS in diabetes ranges from 8% to 53% (20,21,22,23,24,25,26,27). Most studies suggest a prevalence of about 35% in patients with diabetes (28,29,30,31). It is more common in patients with type 1 diabetes and may be associated with duration of disease. The onset of DHS may not be related to the patient’s sex or insulin dosage. It is unclear whether the onset of cheiropathy is related to metabolic control. Silverstein et al. (32) have shown that poor long-term glycemic control, as measured by elevated hemoglobin A_1c levels, does increase the risk of earlier onset of hand symptoms in patients with type 1 diabetes. Clinically, patients complain of stiffness, loss of dexterity, and weakness of their hands. The skin on the hands is typically thick, tight, and waxy, and changes may appear compatible with scleredema. There is evidence of recurrent tenosynovitis and decreased range of motion of the small joints of the hands. The patient may exhibit the prayer sign, that is, when asked to hold the palms of the hands together, the patient is unable to bring the fingers and palms together because of flexor tendon contractures. Limitation of flexion and extension occurs predominantly in the proximal interphalangeal and metacarpophalangeal joints. Decreased grip strength results. Sclerodactyly and thick skin may be present.

Much has been reported about the relationship of DHS with the age of the patient, the duration of diabetes, and the presence of diabetic retinopathy (12,29,33,35). In general, DHS is more common in patients with long-standing diabetes and microvascular disease. The presence of DHS may indicate that the patient is at high risk for microvascular disease. In patients with diabetes for 16 years, the prevalence of observed microvascular lesions was three- to fourfold higher in those with hand contractures than in those without contractures (29,33,34,35,36). There is some evidence that joint contractures in patients with diabetes are linked with delayed median-nerve conduction and intrinsic hand-muscle wasting (37,38,39).

In addition, a form of restrictive lung disease has been described in patients with DHS in which total and vital lung capacity is decreased (20,24,25,26). These patients are usually asymptomatic but may experience dyspnea secondary to
hypoxemia. It is likely that in some instances similar abnormalities in connective tissue occur in the hand and the lung.

The limitation of joint movement probably results from dermal and subcutaneous sclerosis (30,40,41). In addition, the fibrous thickening of the flexor tendon sheaths contributes to the loss of mobility. The pathogenesis of these altered connective tissues remains obscure. Pathologically, a biopsy of the thickened skin reveals dermal fibrosis with increased collagen deposition in the dermis and loss of sebaceous glands and other secondary skin appendages (29,31). Raynaud phenomenon, digital ulcers, or other systemic manifestations of scleroderma or other autoimmune diseases are not present. Laboratory evaluation is unrevealing, and radiographs of the hands may be normal or show diffuse osteopenia. Some investigators have documented increased cross-linking of collagen, which leads to increased resistance to collagenase and the resultant decrease in turnover (42,43,44). Increased nonenzymatic glycosylation of collagen, which might increase intermolecular cross-linking, has also been demonstrated (45,46,47,48,49,50,51). Other possible factors include increased hydration of collagen, swelling of the connective tissue through the aldose reductase pathway, and microangiopathy leading to increased collagen synthesis.

Importantly, the role of sorbitol has been hypothesized as possibly contributing to the microvascular complications in patients with diabetes. Hyperglycemia promotes increases in the amount of sorbitol accumulating in cells. In cells, glucose is converted to sorbitol via the enzyme aldose reductase, which may be responsible for an increase in cell osmolality, decreased cell myoinositol, and other factors that may promote collagen and connective tissue abnormalities (52,53,54). Thus, if sorbitol plays a major role in collagen dysregulation or tissue damage, the use of aldose reductase inhibitors in patients with diabetes may decrease the accumulation of sorbitol and subsequently decrease the microvascular and collagen complications of diabetes. Clinical trials of aldose reductase inhibitors have not shown consistent improvement in the microvascular complications, such as retinopathy, neuropathy, and nephropathy (52,53,54). There is one report of three patients with contractures who demonstrated a reversal of hand symptoms with aldose reductase inhibitors (55).

Another proposed mechanism is the accumulation of advanced glycosylated end products (AGEs) that may predispose to collagen abnormalities and tissue injury (56,57). Hyperglycemia provides an environment of enhanced glucose availability that accelerates the deposition of AGEs into tissues. This may lead to a stronger cross-linking potential of collagen in vivo and vascular injury, as endothelial cells have receptors for AGEs. Clinical trials are now being conducted on aminoguanidine, an agent that prevents the deposition of AGEs in tissue, for the prevention of diabetic nephropathy (58). Perhaps future studies will be undertaken for DHS.

Therapy for the diabetic hand syndrome should include dynamic splinting and an attempt to increase range of motion through exercise. It is unclear without prospective studies whether an increase in exercise will prevent the onset of limited joint mobility or will restore joint mobility that has been lost. Aspirin, NSAIDs, or opiate analgesics for those who are not responding to local modalities may be helpful in controlling pain and stiffness. There are case reports in the literature suggesting that better glycemic control may lead to a decrease in skin thickness (59).

Dupuytren disease is common in the general population and increases in incidence as the population ages (3,60). It causes a focal flexion contracture with a thickened band of palmar fascia. Flexion deformities along with tethering of the skin are noted. Knuckle pads (Garrod pads), as well as heel-pad nodules, may be noted (3). Pain and loss of motion result. Dupuytren contracture, in which a low-grade inflammatory reaction producing nodularity may occur, often is associated with diabetes. Contractures may involve the third, fourth, or fifth flexor tendons.

It has been suggested that 25% of patients with Dupuytren contractures have diabetes (2,61). In addition, studies have shown that 21% to 63% of patients with diabetes have the contractures, in contrast to 5% to 22% of the normal population (2). Noble et al. (62) reported the development of this complication in more than 50% of patients with diabetes and an increase in incidence with duration of diabetes and also demonstrated that a high proportion—as high as 16% of adults with diabetes—have Dupuytren contracture at the time of diagnosis of diabetes.

The pathogenesis of Dupuytren disease remains unknown. Occasionally, a history of occupational or other trauma may precede its onset. Investigators have described the occurrence of modified fibroblasts (myofibroblasts) that resemble smooth muscle cells and are contractile within tendon nodules (63,64). Proliferation of these cells with subsequent contraction might subject neighboring fascial structures to intermittent tension, resulting in hypertrophy. These same cells have also been reported in the nodules of patients with Ledderhose disease and may be present in the abnormal tissues of patients with Peyronie disease (65,66).