Tai chi training appears to be effective as a stand-alone behavioral intervention for reducing balance impairments in patients who have mild to moderate Parkinson disease. Improved functional capacity and reduced incidence of falls are other potential benefits.

Li and associates conducted a randomized controlled trial of 195 patients to compare the effects of exercise at 6 months in those assigned to twice-weekly tai chi classes with those in resistance-training or stretching groups. The primary outcomes were indicators of postural stability-maximum excursion and directional control. Secondary outcomes included measures of gait and strength and number of falls.

The tai chi group performed consistently better than the resistance-training and stretching groups in maximum excursion and in directional control. The tai chi group also performed better than the stretching group in all secondary outcomes and outperformed the resistance-training group in stride length and functional reach. The incidence of falls was lower in the tai chi group than in the other groups. The effects of tai chi training were maintained at 3 months after the intervention. No serious adverse events were observed.

The authors noted that the changes resulting from tai chi training indicate increased potential for effectively performing activities of daily living.

Articles

Tai chi training appears to be effective as a stand-alone behavioral intervention for reducing balance impairments in patients who have mild to moderate Parkinson disease.

Tai Chi Improves Balance in Parkinson Disease

 Cocaine has been implicated in many rheumatologic conditions. Recognition of these syndromes is important for appropriate diagnosis and management because they often are confused and misdiagnosis results. The principal effects of cocaine are seen in the CNS and the corticomesolimbic dopamine reward pathway. Whether cocaine itself or in combination with host proteins is immunogenic and whether such a phenomenon has clinical relevance is unclear. Levamisole was recently found to contaminate up to 70% of cocaine samples; it has been postulated to cause various cutaneous lesions. Cocaine-induced midline destructive lesions have been associated with cocaine. Cocaine may have deleterious effects on the cardiovascular system. Management strategies include making the diagnosis, gaining knowledge of the disorders that cocaine can mimic, and testing for cocaine and levamisole contaminant. (

Thirty million Americans have used cocaine, making the United States the world’s largest consumer of the substance; there are about 5 million current users.

 More than 70% of cocaine samples have been contaminated with levamisole, an immunomodulatory agent associated with multiple medical complications.

Cocaine, especially contaminated cocaine, has been implicated in many rheumatologic conditions, such as cutaneous vasculitis, midline granulomatous lesions, cerebral vasculitis, and coronary aneurysms. Prompt recognition of these syndromes is important for appropriate diagnosis and management because they often are confused and misdiagnosis results. In this article, we describe these syndromes and provide clues that help with early diagnosis and appropriate management of cocaine-induced rheumatologic mimics.

Cocaine is a tropane ester alkaloid found in the leaves of 

, a bush that grows in the Andes Mountains in South America.

 Its stimulant properties have been known to mankind for more than 2000 years. Cocaine has remained a vital part of the religious beliefs of the Andean peoples of Peru, Bolivia, Ecuador, Colombia, and northern Argentina and Chile from the pre-Inca period through the present.

Key events in the history of cocaine include the following:

• In 1596, cocaine was first used for medicinal purposes by a Spanish physician.

• In 1860, cocaine was isolated from the coca leaf by a German graduate student, Albert Niemann, who also is credited with coining the word “cocaine.”

• In 1884, Freud first reported the major effects of cocaine as a stimulant against hunger and fatigue, its efficacy in high-altitude sickness, and its effects as a local anesthetic and hemostatic agent.

• In 1914, the Harrison Narcotic Act designated cocaine as a prescription drug and placed it under Schedule II of the Controlled Substances Act.

There are a reported 14 million cocaine users worldwide.

 In 2002 and 2003, more than 5.9 million persons (2.5%) aged 12 years or older admitted to using cocaine within the previous year. In the United States, cocaine use rates ranged from 1.6% in Idaho to 3.9% in Colorado. The annual consumption of cocaine worldwide is about 600 tons; the United States consumes about 300 tons.

The principal effects of cocaine, a monoamine neurotransmitter reuptake inhibitor, are seen in the CNS (vasoconstriction, tachycardia, hypertension, arrhythmias, seizures, mydriasis, hyperglycemia, and hyperthermia) and the corticomesolimbic dopamine reward pathway (acute use of cocaine elevates dopamine levels and causes euphoria; long-term use causes dopamine depletion, leading to dysphoria and craving). Cocaine also blocks sodium-gated ion channels, causing cardiac arrhythmias and local anesthetic effects. Cocaine-induced arterial spasm may cause endothelial injury and promote platelet aggregation and adherence.

Whether cocaine itself or in combination with host proteins is immunogenic and whether such a phenomenon has clinical relevance are unclear. According to Deng and associates,

 however, cocaine covalently modifies proteins through a reaction where the methyl ester acylates the ε-amino group of lysine residues. Plasma samples from long-term (14 ± 3 years) cocaine users and controls were analyzed for anti-cocaine antibodies; they were detected in 2 of 7 cocaine users and in none of the controls. The authors concluded that modification of endogenous proteins by the benzoylecgonine moiety of cocaine could produce an immunogen that might explain some of the drug’s autoimmune effects.

Additional studies in preclinical models also have demonstrated nonspecific immunological effects of cocaine on both innate and adaptive immune responses.

 However, the clinical implications of these phenomena remain unclear.

Cutting, or “stepping on,” cocaine is common, and compounds are used (eg, novocain, ephedrine, caffeine, methylphenidate, and inactive sugars) that simulate ingestion effects. The recent finding that levamisole (a synthetic imidazothiazole derivative) contaminates up to 70% of cocaine samples probably is the result of the effort to increase the bulk of the cocaine because of the high cost and demand for the drug. Levamisole is thought to enhance the euphoric effects of cocaine because of inhibition of dopamine reuptake in the presynaptic neurons.

Levamisole was first reported as a contaminant by the US Drug Enforcement Administration in 2008.

 It is a powerful immunomodulatory agent that has been used as adjuvant therapy for adenocarcinoma of the colon, in relapsing nephrotic syndrome in children, and as a slow-acting antirheumatic medication for patients with rheumatoid arthritis (RA). Levamisole may restore depressed immune function and stimulate antibodies by increasing T-cell activation and proliferation and increasing neutrophil mobility, adherence, and chemotaxis.

Levamisole was withdrawn from the market in 2000 because of adverse effects, including neutropenia, cutaneous ulcers/vasculitis, convulsions, hypogammaglobulinemia, and arthralgias. It currently is used only in veterinary medicine as an antihelminthic medication. Levamisole may be detected in urine and blood only by gas chromatography and mass spectrometry within 48 hours of contaminated cocaine use.

Levamisole has been postulated to cause various cutaneous lesions, such as nodules, drug eruptions, palpable purpura, and ulcers. The first case of levamisole-induced cutaneous vasculitis was reported in 1978 in a 59-year-old woman who was receiving levamisole 150 mg/d 3 times a week for 3 months for breast cancer.

 Fever, neutropenia, and rash developed, and a skin biopsy revealed vasculopathy. The symptoms resolved within 2 weeks after discontinuation of the drug and a short course of prednisone.

These lesions, which have a peculiar predilection for the ear lobules and cheeks, also have been observed when levamisole has been used as adjuvant therapy for pediatric nephritic syndrome and as a slow-acting antirheumatic agent for RA. They have been reported to appear between 12 and 44 months after the introduction of levamisole.

 Patients also have concurrent neutropenia and autoantibodies.

In our opinion, levamisole is the likely culprit in most cases of cocaine-related cutaneous lesions. As mentioned above, the immunomodulatory effects of levamisole probably contribute to the clinical features.

Cocaine is about 90% plasma-bound; the plasma half-life is short, ranging from 0.5 to 1.5 hours. About 90% of a cocaine dose is metabolized to its major metabolites-ecgonine methyl ester and benzoylecgonine.

Cocaine may be detected in urine up to 2 to 4 days after consumption and its metabolites for 6 to 14 days after illicit drug use.

 It may be detected in body fluids and tissues, such as urine, hair, saliva, sweat, nails, pericardial fluid, vitreous humor, and organs (brain/muscle/bones). Urine drug screens are performed frequently because of their convenience, low invasiveness, and accuracy and the higher concentrations of the drug in urine than in blood or plasma.

The screening test is done by immunoassay and confirmed with gas chromatography-mass spectrometry.

 Hair analysis represents an alternative for cocaine testing because the drug may be detected for weeks to months after use. Oral fluid analysis detects non–protein-bound cocaine and may detect the drug up to 17 hours after the last dose.

Cocaine (and its contaminants) may present in ways that mimic a number of rheumatologic conditions and cause diagnostic confusion. Conditions that have been associated with cocaine include the following:

 
Cocaine-related cutaneous lesions are shown in these photographs. (Reproduced with permission from Chung C et al. 

. Cocaine always should be considered as a possible cause of unexplained skin lesions in vulnerable patient populations (

). The most characteristic rash associated with cocaine is that of cutaneous necrosis, especially when it involves the face, including the ears and nose (

 
Case reports and series of cocaine-induced cutaneous lesions

A similar rash may be seen in patients with cryoprotein disorders, coagulopathies, systemic vasculitis, and frostbite, as well as other conditions. Epidemiologically, however, cocaine and levamisole exposure ranks high in the differential diagnosis (

Warfarin-induced skin necrosis may be confused with cocaine-related cutaneous lesions. This entity may be seen in obese women, typically those who are protein C– or protein S–deficient, within 1 to 10 days of warfarin exposure. Warfarin-induced skin necrosis often involves fatty areas of the body, such as the breasts, buttocks, and thighs. The lesions consist of bullae and necrosis; skin biopsy reveals bland thrombi.

 
Differential diagnosis of cocaine/levamisole-induced toxicity

Heparin-induced cutaneous necrosis, a rare manifestation of heparin-induced thrombocytopenia, also causes tender, noninflamed lesions on the abdomen and extremities. It usually is seen 4 to 10 days after initial exposure to heparin. Skin biopsy shows bland thrombi.

 The pathophysiology of some of these lesions is unclear because they are similar to the skin lesions ascribed to levamisole and thus may be immune-mediated. Alternatively, cocaine itself may play a role because of its vasoconstrictive effects on the small vessels, especially in peripheral areas such as the ears.

. Cocaine-induced midline destructive lesions (CIMDL), a syndrome of extensive destruction of the nose, palate, and midline structures, recently was associated with cocaine. A 2004 study tested human neutrophil elastase (HNE) antineutrophil cytoplasmic antibodies (ANCAs) reactivity in 25 patients with CIMDL.

 The controls consisted of 604 consecutive patients who had granulomatosis with polyangiitis (GPA) (formerly known as Wegener granulomatosis), microscopic polyangiitis (MPA), or another rheumatologic disorder and healthy volunteers. HNE ANCAs were detected by indirect immunofluorescence and direct and capture enzyme-linked immunosorbent assay.

In patients who had CIMDL, HNE ANCAs were detectable in 84% by 1 assay, in 68% by 2 assays, and in 36% by 3 assays. Of HNE ANCA–positive CIMDL sera, 57% were positive for proteinase 3 (PR3) ANCA by at least 1 assay. Only 1.3% of controls reacted with HNE in at least 1 assay, 0.5% in 2 assays, and 0.16% in 3 assays. The sera of patients with GPA or MPA and healthy volunteers were negative for HNE ANCAs. The authors concluded that optimal sensitivity for HNE ANCAs requires multimodality testing; HNE ANCAs are frequent in CIMDL but not in classic ANCA-associated vasculitis.

The mechanism of action of cocaine in such cases may be related to the production of HNE ANCAs. HNE and PR3 are part of the chymotrypsin family of serine proteinases. HNE ANCAs may activate primed neutrophils, modify clearance of apoptotic cells, and enhance or perturb neutrophil apoptosis. A high frequency of apoptotic cells has been described in CIMDL.

Cocaine has a vasoconstrictive and irritant effect that may lead to inflammation, ulceration, erosion, and disintegration of the nasal septum-with bleeding and perforation-leading to a saddle nose deformity. There also may be ischemic necrosis of the hard and soft palates and recurrent infection with 

Cocaine-induced cerebral vasospasm and “vasculitis.”

 Cocaine has multiple effects on the CNS, causing ischemic and hemorrhagic strokes that primarily result from vasospasm, cerebral vascular thrombosis, enhanced platelet aggregation, and sporadic episodes of hypertension. Endothelin-1 may be an important mediator in cocaine-induced vasospasm.

The intracerebral syndrome most frequently associated with cocaine is reversible cerebral vasoconstriction syndrome (RCVS).

 This disorder is characterized by prolonged but reversible vasoconstriction of the cerebral arteries that usually is associated with a severe, acute onset and recurrent headaches; other neurological features may be present. Diagnostic features, as suggested by Calabrese and colleagues,

 include radiographic evidence of multifocal segmental cerebral artery vasoconstriction (conventional, CT, or MR angiography), an absence of subarachnoid hemorrhage, normal results of cerebrospinal fluid analysis, severe acute headaches, and reversibility of the angiographic abnormalities within 12 weeks of onset.

Drug-induced cerebral artery vasospasm, such as with cocaine, is a major consideration in the differential diagnosis. Management consists of empiric therapy with calcium channel blockers (nimodipine and verapamil) or other agents; short courses of corticosteroids; magnesium sulfate; or clinical observation.

Cerebral vasculitis also has been postulated to play a role in the neurovascular effects of cocaine. In 1995, Merkel and coworkers

 reviewed 8 cases of cocaine-induced cerebral vasculitis; patients’ mean age was 28 years. Time between last known cocaine use and brain biopsy varied from hours to 6 months. In 6 cases, a brain biopsy revealed small-vessel angiitis. One patient died, and autopsy showed no medium- or large-vessel vasculitis. The authors attributed this complication of cocaine use to the chemical mediators released in the context of endothelial inflammation and a cytokine cascade with resultant vasospasm and arteritis.

Two studies published in 1996 reviewed autopsy samples from cocaine users with fatal cerebral hemorrhages (14 autopsy cases in one and 10 in another). Subarachnoid, intracerebral, or parenchymal hemorrhages were seen in all the specimens, but there was no evidence of vasculitis.

Cocaine may have multiple deleterious effects on the cardiovascular system. Acute use may increase blood pressure and heart rate via α- and -adrenergic stimulation (increased oxygen demand) and coronary spasm via α-adrenergic stimulation (decreased oxygen delivery), resulting in ischemia, infarction, and arrhythmias. Long-term cocaine use may lead to accelerated atherosclerosis, myocarditis, contraction-band necrosis, and dilated or hypertrophic cardiomyopathy

Cocaine always should be included in the differential diagnosis in patients who have appropriate epidemiological risks and a picture of RCVS or unexplained cerebral arteritis; skin lesions; oronasal/palatal destructive deformities, with no systemic features; neutropenia/granulocytosis; and a number of autoimmune laboratory abnormalities. A skin biopsy may be helpful in some patients; this biopsy may reveal vasculopathy, thrombosis, or leukocytoclastic vasculitis.

Cocaine also has been implicated anecdotally in urticarial vasculitis, Churg-Strauss vasculitis, Henoch-Schnlein purpura, lupus and lupus nephritis, Stevens-Johnson syndrome, and antiphospholipid antibody syndrome.

 Skin lesions generally resolve over 2 to 3 weeks after cocaine/levamisole is stopped, and the autoimmune laboratory abnormalities generally resolve over 2 to 12 months.

Cocaine may mimic myriad medical conditions, especially rheumatologic conditions. Whether cocaine itself or the levamisole contaminant causes the autoimmune response remains unclear. Management strategies include making the appropriate diagnosis, gaining knowledge of the various rheumatologic disorders that cocaine can mimic, conducting prompt testing for cocaine and levamisole contaminant, and advocating immediate cessation of cocaine use.

Laboratory testing may consist of a complete blood cell count, basic chemistries and urinalysis with toxicology, and appropriate imaging; when patients present with altered mental status or focal neurological symptoms, lumbar puncture with imaging needs to be considered. Consultation with various medical subspecialties, such as rheumatology, infectious disease, neurology, and dermatology, should be considered. Patients with neutropenia should be monitored for infections and treated appropriately.

The role of corticosteroids in these cases is controversial; they may be used for a short duration to help resolve localized inflammatory features. The use of other immunosuppressive medications, especially over the long term, is strongly discouraged. However, if there is diagnostic confusion as with cerebral vasculitis resulting from cocaine versus other causes, strong immunosuppression should be considered while the workup is under way. Thus, familiarity with the vast array of cocaine-induced conditions is critical for practicing rheumatologists so as to spare patients unnecessary and potentially toxic immunosuppressive therapies.

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 Deng SX, Bharat N, Fischman MC, Landry DW. Covalent modification of proteins by cocaine. 

 Jankowski MM, Ignatowska-Jankowska B, Glac W, Swiergiel AH. Cocaine administration increases CD4/CD8 lymphocyte ratio in peripheral blood despite lymphopenia and elevated corticosterone. 

 Casale JF, Corbeil EM, Hays PA. Identification of levamisole impurities found in illicit cocaine exhibits. 

 Rongioletti F, Ghio L, Ginevri F, et al. Purpura of the ears: a distinctive vasculopathy with circulating autoantibodies complicating long-term treatment with levamisole in children. 

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Recognizing Rheumatologic Aspects of Cocaine Abuse

 Eosinophilic fasciitis (EF) often is confused with scleroderma. A 50-year-old woman presented with progressive tightening of the skin of the arms and legs. She complained of diffuse joint pain that was prominent in the hands and wrists. Her past medical history was significant for hypothyroidism. A skin biopsy revealed superficial and deep infiltrates of inflammatory cells with eosinophils. Physical examination findings were significant for skin hypopigmentation and hyperpigmentation over her forearms and legs. EF may be difficult to differentiate from localized scleroderma, limited and diffuse cutaneous systemic sclerosis, and several scleroderma-like disorders. (

Eosinophilic fasciitis (EF), also known as Shulman disease and diffuse fasciitis with eosinophilia, is an uncommon condition that often is confused with scleroderma because they have similar features. Shulman

 first described EF in 1974 when he saw patients with scleroderma-like skin changes but histopathological features on deep biopsy showed evidence of diffuse fasciitis. In this article, we describe an unusual case of a patient who presented to our academic clinic for consultation with either scleroderma or severe, advanced morphea.

A 50-year-old white woman presented to our clinic with progressive tightening of the skin of the arms and legs that had started 8 months earlier when she was packing with her family to move to Florida. She stated that the packing took too many long hours and was very strenuous. She had noticed a hardened patch of skin on her left lower leg above the ankle, but she did not recall experiencing any injury to that area while she was packing.

Progressive hardening of her arms and legs with hypopigmented and hyperpigmented skin developed gradually over a few months but spared her hands and feet. She complained of joint pain that was diffuse but was prominent in the hands and wrists, which appeared swollen and puffy. She denied any history of Raynaud phenomenon (RP), shortness of breath, chest pain, fatigue, or dysphasia.

The patient started to receive 10 mg/d of prednisone a few months later, and her joint pain, swelling, and arthritis resolved completely. However, the skin tightness continued to progress to involve the whole arms and legs while sparing the trunk, face, hands, and feet. Some areas of the skin on her upper arms and thighs appeared “to have hardened wrinkles or to be cellulite-like in the thigh area,” as the patient described it.

The patient’s past medical history was significant for hypothyroidism. That diagnosis had been made 7 years earlier, when she was working as a respiratory therapist at a hospital in Virginia and was complaining of progressive fatigue.

She denied having had any similar skin lesions in the past. However, 7 years earlier she had had one area of erythema and slightly hardened skin over her right ankle. It was itchy but resolved in a few months without complications or scarring. Her treating physician told her at the time that she had morphea.

The patient is married and has 6 children. She denied any history of drug, alcohol, or tobacco use, and her family history was negative for any autoimmune connective-tissue disease. Otherwise, findings from a review of systems were completely unremarkable. She was taking only the prednisone at 10 mg/d, her thyroid replacement medication, a multivitamin, and fexofenadine as needed for chronic seasonal allergies.

A skin biopsy specimen was obtained from the patient’s right forearm at the time when her joint symptoms had resolved. It revealed superficial and deep infiltrates of inflammatory cells with eosinophils. Blood work done a month earlier showed a negative antinuclear antibodies (ANAs) test result and normal thyroid-stimulating hormone and creatine phosphokinase levels. Tests for extractable nuclear antigen, anticentromere, Scl-70, Jo-1, and thyroid peroxidase antibodies were performed before her visit, and the results were negative. Also, her erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and aldolase levels were within normal limits.

Findings from the patient’s physical examination were significant for hypopigmentation and hyperpigmentation of her skin over her forearms and legs. The skin was tight; her hands and feet were spared. Multiple “orange peel,” or “peau d’orange,” signs (normal skin color with the dimpled appearance of an orange peel) and “groove” signs (dimpling of the medial upper arm with elevation, leaving an indentation on the overlying skin

) were elicited. Findings from the rest of the physical examination were unremarkable.

The consulting physician requested a differential between a possibly advanced morphea and an atypical presentation of scleroderma. After examining the patient and reviewing her history, we concluded that she probably had EF.

Deep tissue biopsy had been planned by the patient’s dermatologist, but her insurance did not cover it and it was not obtained. However, this is a classic case with the sparing of the hands and feet and the physical examination findings. The initial skin biopsy, not a deep tissue biopsy, specimen showed increased eosinophils. In early, evolving, or atypical cases, a deep tissue biopsy might be needed to confirm the diagnosis; this did not apply to our patient, who presented with an established, advanced, and classic case.

EF is a rare fibrosing disorder that presents as skin edema and thickening followed by indurations.

 Histopathological findings early in the disease course show involvement of the deep fascia and lower subcutaneous tissue. Infiltration of lymphocytes, plasma cells, histiocytes, and eosinophils is observed on biopsy. In addition to involvement of deep fascia and subcutaneous tissue, the dermis becomes thickened and sclerotic and inflammatory cell infiltrates disappear.

 A history of strenuous exercise preceding the development of symptoms may be reported in up to 50% of patients with EF.

The clinical manifestations of EF usually occur in 3 stages. The first stage involves pitting and edema of the affected skin; a peau d’orange appearance and indurations and the groove sign are seen in the second stage. The arms and legs are the most frequently affected sites. The hands and feet usually are spared in EF, in contrast to scleroderma, in which the hands are involved in nearly all cases.

In the third stage, there may be periarticular involvement and atrophy of muscles that may result in flexion contractures and functional disability. Peripheral nerves also may be involved, leading to nerve compression and carpal tunnel syndrome.

RP is present in nearly all patients who have systemic sclerosis (SSc) but is typically absent in EF, as in our patient. True sclerodactyly and nailfold capillary abnormalities do not occur in EF. Peripheral eosinophilia has been documented in up to 80% of patients in the early disease stages, but this and polyclonal hypergammaglobulinemia could disappear in the later stages. The ESR and CRP level also may be elevated in EF. Hematological malignancies and, in some case series, autoimmune thyroid disease have been associated with EF.

 The absence of RP and lack of sclerodactyly should alert the physician to consider a scleroderma-like disorder.

MRI has emerged as an important tool for evaluation of EF. On MRI, characteristic signs may be observed, such as facial thickening, hyperintense signal within the fascia on fluid-sensitive sequences, and facial enhancement after contrast. MRI also helps identify the area for deep skin biopsy. Deep skin biopsy usually is required to differentiate among erythema nodosum, bite reaction, parasitic reaction, and Well syndrome, in which eosinophilia is limited to the superficial layers.

Treatment for patients with EF is limited.

 Corticosteroids are first-line agents and usually are given in moderate to high doses. No controlled trials have determined the efficacy of different dosing, but the current concensus is to use up to 1 mg/kg of prednisone, with tapering tailored to the response. The duration of the therapy varies with the resolution of the symptoms.

In patients who do not respond to corticosteroids, immunosuppressive therapy (eg, methotrexate [MTX], cyclosporine, hydroxychloroquine, and psoralen and UV-A light therapy [photochemotherapy]) have been used. However, the results have not been consistent, as they are with corticosteroids.

The mortality rate for patients with EF remains low. Recurrence has been documented in the literature, but data on the percentage of patients who experience relapse are lacking.

EF may be difficult to differentiate from localized scleroderma, limited and diffuse cutaneous SSc, and several scleroderma-like disorders. RP usually is absent in EF. An overwhelming majority of patients with both limited and diffuse cutaneous forms of SSc have RP or it develops at or near the time of the earliest skin changes.

Nailfold capillaries exhibit dilated capillary loops and avascular areas by capillaroscopy in SSc, which typically are normal in EF.

 The fingers, feet, and face are spared in EF but usually are involved in most forms of limited and diffuse SSc. Internal organ involvement (eg, pulmonary fibrosis, pulmonary hypertension, renal crisis) is frequent in SSc but typically is absent in EF. Unlike SSc, EF is not associated with serum ANAs or SSc-specific autoantibodies.

Nephrogenic systemic fibrosis (NSF) occurs in patients with advanced renal failure (dialysis-dependent or estimated glomerular filtration rate lower than 15 mL/min) after the administration of gadolinium and perhaps erythropoietin; the clinical manifestations of this syndrome resemble those of EF.

 NSF may be distinguished from EF by involvement of the hands and feet and the absence of eosinophilia and eosinophilic tissue infiltration in patients with advanced renal failure.

Scleromyxedema, an idiopathic disorder, may occur alone or in association with malignancies. Skin thickening results from deposition of an amorphous mucinous material in the dermis.

Palmar fasciitis and polyarthritis syndrome is an uncommon paraneoplastic presentation that was first described in 1982.

 An association was found between palmar fasciitis and polyarthritis syndrome and ovarian carcinoma; this was described as a variant of reflex sympathetic dystrophy (RSD). Palmar fasciitis and polyarthritis syndrome can mimic other conditions, including scleroderma; complex regional pain syndrome (CRPS), or RSD; Dupuytren disease; and EF.

In palmar fasciitis and polyarthritis syndrome, there is an absence of RP and a lack of specific autoantibodies. The condition is characterized by rapid progression of clinical features, which helps exclude scleroderma; the synovitis and indurated swelling of digits and the rapid progression of clinical features of the hand make Dupuytren disease an unlikely diagnosis. In contrast to CRPS, palmar fasciitis and polyarthritis syndrome almost always presents with bilateral inflammatory arthritis and fasciitis that is not localized to a particular limb, and it usually has a more severe presentation that typically involves both palms while sparing the dorsal surface of the hands. Patients typically are referred to rheumatology as “scleroderma,” although they need an immediate oncology evaluation and have a very poor prognosis.

The pathology of skin and subcutaneous tissue in eosinophilia-myalgia syndrome (EMS) cannot be differentiated from that in EF. Some features may be valuable in distinguishing one condition from the other. Most cases of EMS have resulted from exposure to a contaminant of L-tryptophan, which principally had been used to manage insomnia.

EMS occurs in clusters, and sporadic forms are rare. Myalgias, often severe, have been seen frequently in EMS and remain a criterion for classification. Nonpitting edema that evolves into induration with a peau d’orange appearance in EMS is similar to that seen with EF.

 Visceral involvement is seen more often in patients with EMS than in those with EF.

Adulterated rapeseed oil was associated with an epidemic of EMS-like illness in Spain.

 In its natural form, rapeseed oil may be somewhat toxic to humans because it contains a significant amount of erucic acid.

Characteristic symptoms the EMS-like illness are myalgia, arthralgia, and dyspnea. Physical findings include limb swelling, chronic scleroderma-like skin changes, livedo reticularis, neuropathy, and joint contractures. Pulmonary infiltrates and prominent eosinophilia are other features present in EMS.

The patient received prednisone 10 mg/d initially; there was poor response in the skin and underlying tissue but complete resolution of arthritis. The prednisone dosage was increased to 10 mg tid for 2 months, and there was a great response and improvement of tight tissues. Then the prednisone dosage was lowered to 10 mg bid for 2 months, then 5 mg tid for 2 months, then 5 mg bid for 2 months. Treatment with MTX was started and increased to 15 mg/wk after a few weeks.

The patient had been receiving MTX for 10 weeks and prednisone at 5 mg/d for the previous 2 weeks when we examined her at follow-up. We noted a dramatic and significant improvement in her skin condition. The MTX dosage was increased to 17.5 mg/wk; the patient will be weaned off the prednisone completely and gradually over 4 weeks.

This case confused many physicians, who all agreed that the patient had what appeared to be tight skin, because it is rare. Clinicians should recognize the atypical features of SSc, which should trigger the search for mimickers. The patient lacked RP, which is typical of SSc or ANA-related diseases, and lacked dactylitis, which is another feature of ANA-related sclerosing conditions. Localized scleroderma was suggested, but the diffuse involvement, despite its possibility, was unusual, except in some rare cases in which there could be internal organ involvement and ANA positivity.

The big clue is that clinically this is not scleroderma or skin tightness or thickening. The pathology is in the fascia below the skin, which typically is spared in the hands and feet. It is not a vasculopathy and, hence, the absence of RP.

A closer look at the physical examination findings and targeted history clearly point away from scleroderma and should direct the examiner to other mimickers. This is critical, because the clinical course, prognosis, and treatment are completely different from those of scleroderma, which could have a much worse outcome and could require much more toxic treatments.

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Eosinophilic fasciitis (EF), also known as Shulman disease and diffuse fasciitis with eosinophilia, is an uncommon condition that often is confused with scleroderma because they have similar features.

Eosinophilic Fasciitis: A Difficult Diagnosis

A healthy 40-year-old active-duty male soldier presented with a painless groin mass, which he had noted a few weeks earlier. He denied having constitutional symptoms, recent infection, inflammatory joint symptoms, or a history of trauma.

The physical examination was notable for an immobile firm mass in the patient’s right inguinal area. There were no other areas of lymphadenopathy, and the results of a genitourinary examination were normal.

Radiographs of the patient's right hip and pelvis were obtained; the results were unremarkable. An ultrasonogram (top) and an MRI scan (bottom) were obtained. What do they show?

To learn the nature of this groin mass, click here.

A healthy 40-year-old active-duty male soldier presented with a painless groin mass, which he had noted a few weeks earlier.

Painless Groin Mass in an Active-Duty Soldier

Statins help reduce total cholesterol (TC) concentrations in patients with osteoarthritis (OA) or rheumatoid arthritis (RA). The use of statins is associated with reduced cardiovascular (CV) events and mortality in patients with RA and reduced mortality in those with OA in primary prevention.

Sheng and associates conducted a population-based cohort study of patients with OA or RA who had at least 2 separate TC measurements. The patients were categorized in statin-exposed and statin-unexposed groups according to statin use status during follow-up. The primary study outcome was TC concentration change from baseline; the secondary outcomes were CV events and all-cause mortality during the follow-up.

Statin-associated TC concentrations in OA and RA decreased from baseline by 15% and 16%, respectively, in patients without CV disease and by 7% and 15%, respectively, in patients with CV disease. There were protective effects of statins on CV mortality and all-cause mortality in patients with OA and on CV events and all-cause mortality in patients with RA in primary prevention.

The authors noted that statins were not associated with a reduced risk of CV events or all-cause mortality in secondary prevention and that the persistence of statin treatment was not taken into consideration in the study.

Statins help reduce total cholesterol (TC) concentrations in patients with osteoarthritis (OA) or rheumatoid arthritis (RA).

Statins Reduce Cardiovascular Events in OA and RA

Disease burden in patients with a new diagnosis of systemic lupus erythematosus (SLE) changes over the first 5 years. Disease activity decreases and remains at a low level, but damage, especially damage related to corticosteroid therapy, accumulates.

Urowitz and colleagues monitored an inception cohort of 298 patients from the Systemic Lupus International Collaborating Clinics (SLICC) International Research Network for a minimum of 5 years. They assessed disease activity with the SLE Disease Activity Index 2000 (SLEDAI-2K) and damage with the SLICC/American College of Rheumatology Damage Index (SDI). Antinuclear antibody (ANA), anti-DNA, and anticardiolipin antibody levels and lupus anticoagulant were assessed.

Mean SLEDAI-2K scores decreased in the first year and remained low; scores were significantly lower in white patients than in nonwhite patients. Mean SDI scores increased progressively over 5 years with no significant difference between white and nonwhite patients. Damage resulting from corticosteroids increased over the 5 years. At enrollment, ANA positivity was high and anti-DNA positivity was somewhat low; both increased over 5 years.

The authors noted that in this study, the damage resulting from corticosteroids did not increase as dramatically as in previous years, possibly reflecting a more judicious use of these agents in the current era.

Disease burden in patients with a new diagnosis of systemic lupus erythematosus (SLE) changes over the first 5 years.

Lupus Disease Activity Decreases, but Damage Accumulates

There is a strong dose-dependent association between sleep problems and the risk of fibromyalgia syndrome (FMS) in women. The association is stronger in middle-aged and older women than it is in younger women, although not significantly stronger.

Mork and Nilsen longitudinally studied 12,350 women who did not have FMS, musculoskeletal pain, or physical impairment at baseline. The patients were asked to report physician-diagnosed FMS and duration of musculoskeletal pain. Sleep problems at baseline were assessed.

Sleep problems were positively associated with the risk of FMS in a dose-dependent manner. In the overall study population, the adjusted risk ratio (RR) for FMS development was 3.43 among women who reported experiencing sleep problems often or always, compared with women who did not have sleep problems. Women who reported experiencing sleep problems sometimes had a 2-fold increase in risk of FMS. Women aged 45 years and older and those aged 20 to 44 years who often or always had sleep problems had adjusted RRs for FMS development of 5.41 and 2.98, respectively, compared with those without sleep problems.

The authors suggested that future studies investigate whether early detection and management of sleep problems can reduce the risk of chronic widespread pain.

There is a strong dose-dependent association between sleep problems and the risk of fibromyalgia syndrome (FMS) in women.

Sleep Problems Increase Fibromyalgia Risk

 Performing exercises can help patients maintain or improvethe range of motion of various joints, improve balance, support function, prevent bone tissue demineralization, lower blood pressure and cholesterol levels, and improve mood. Some familiarity with the histophysiology of the muscular system and the biochemistry of muscle work is needed to understand the implications of exercising and appropriately advise patients who have musculoskeletal disorders. Exercises may be divided into 2 groups: static and dynamic. Specific exercises may be classified as isometric, isotonic, or isokinetic. Exercises also may be classified clinically as active, active assistive, or passive. Muscle strength may be graded with the use of a system based on the muscle’s ability to move against gravity or a specific resistance. ( 

Exercises to promote strengthening, conditioning, and pain control are prescribed regularly as part of the “medical armamentarium.” The literature is full of information indicating that exercise promotes well-being, although it also shows that vigorous exercise may be harmful, as in patients with myopathies.

Exercises can be thought of as body activity that requires physical exertion to develop, maintain, or increase fitness and skill. The performance of exercises can help maintain or improve the range of motion of various joints, improve balance, support function, prevent bone tissue demineralization, lower blood pressure and cholesterol levels, and improve mood. However, some familiarity with the histophysiology of the muscular system and the biochemistry of muscle work is needed to understand the implications of exercising and appropriately advise patients who have musculoskeletal disorders.

In this article, we provide a review of the histophysiology and biochemistry of muscle work. We also describe exercise goals and types.

Human skeletal muscles are composed of 2 types of fibers. They are type 1, or red, and type 2, or white, fibers.

These are called red fibers because of the high content of myoglobin and capillaries (hence, blood). They also are referred to as slow-twitching fibers because they demonstrate a rather slow speed to contraction and relaxation time compared with type 2 fibers. They produce their energy anaerobically and tire when their fuel supplies are gone. They have a large number of mitochondria to accommodate the oxidative phosphorylation processes needed for aerobic metabolism.

The aerobic pathway, which is very efficient, is needed in activities that require endurance. Therefore, the generated force is not explosive but rather submaximal and continuous, as when a person performs high-repetition, low-load activities.

Mitochondria are rod-shaped organelles in the cell cytoplasm. Through enzymatic activity, they convert oxygen, fatty acid, and glucose into adenosine triphosphate (ATP), the chemical energy necessary for the cell’s metabolism.

These are called white fibers because they lack a large number of capillaries and myoglobin and are fast-twitching. They are subdivided into type 2a and type 2b; type 2a fibers contain a larger concentration of oxidative enzymes than type 2b fibers.

Type 2b fibers generally are the fibers of anaerobic energy (ability to work), strength (physical energy), and power (ability to produce an effect). They contract quickly, yielding short bursts of energy, so that they are recruited mostly for brief and intense exercise (eg, sprinting and swimming). Because these fibers depend on anaerobic energy, they become vulnerable to the by-products of their own metabolism as increasing levels of work are performed: using glycolysis to produce ATP elevates metabolic lactic acid levels in the cell, generating muscle fatigue down to exhaustion.

The lactic acid hypothesis remains controversial in scientific review. It has been partially verified by the finding that patients with McArdle disease, who are unable to metabolize glycogen and thus produce lactate, do not exhibit a decrease in sarcolemma conduction velocity during exercise until there is an additional change in force output.

 However, the hypothesis also has been refuted by findings indicating that median power frequency changes and restitution postexercise are unrelated to blood lactate levels.

Another type of fiber, 2m, is characterized by very fast contractions via the glycolytic pathway. These fibers are responsible for very fast movements, such as those of the eye muscles and vocal cords.

In the human body, the proportions of fast- and slow-twitching fibers in all muscle groups are determined genetically. Each muscle group has both types, in varying proportions.

Training can play an important role in the metabolic performance of these fibers. For example, a trained muscle with a high percentage of fast-twitching fibers may perform more efficiently to provide endurance than a deconditioned one with slow-twitching fibers. To a certain extent, therefore, these 2 types of fibers may interchange in their performance. However, the effects of training on a muscle are reversible: once muscle fibers no longer experience resistance or endurance demands, they atrophy rapidly.

Strength is the ability to generate maximal force at some particular moment; muscle endurance is the ability to sustain a submaximal force for an extended period. Physiologically, muscle work can be described as strength or endurance; skill may be a combination of the two.

The fast-twitching fibers are recruited to start a work as inertia is overcome or to produce a change in velocity or direction. If the work requires a low to moderate intensity of work at a constant velocity, then the slow-twitching fibers are used. In reality, if the fast-twitching fibers are mobilized to start a work, they fatigue rapidly, leaving the slow-twitching fibers to sustain the work.

When a muscle is injured, disuse from the injury itself may create atrophy, which results in the fast-twitching fibers rapidly losing size as well as strength; the slow-twitching fibers may retain both size and strength. Therefore, the ratio of strength to endurance ultimately may change, leading to muscle fatigue, which may then favor the development of substitution patterns and poor body mechanics.

The Henneman size principle states that motor units are recruited in an orderly manner from the smaller (lower threshold) to the larger (higher threshold) units and that the recruitment is dependent on the effort of the activity.

 Greater recruitment produces higher muscular force. However, the pervasive faulty assumption that maximal force (very heavy resistance) is required for recruitment of the higher threshold motor units and optimal strength is not supported by the size principle, motor unit activation studies, or resistance training studies. This flawed premise has resulted in the unsubstantiated heavier-is-better recommendation for resistance training.

Muscle motion is fueled by the breakdown of ATP, which generally occurs in a constant fashion. A rapid use of ATP could result in a quick muscle contraction, followed by a period of exhaustion.

This is another controversial topic. Insufficient intramuscular ATP often is thought to be the cause of fatigue, although considerable evidence suggests that this might not be the case. Numerous studies have demonstrated that ATP falls no more than about 70% of pre-exercise levels during high-intensity exercise. However, there is speculation that 70% to 80% of the sarcoplasmic ATP is restricted to the mitochondria and is unavailable to the cross-bridges. In other words, ATP is “compartmentalized” and, although sufficient ATP is inside the cell, it is not in the location where needed. However, a compelling argument against this hypothesis is that tension would develop in resting muscle from rigor cross-bridges because of a lack of ATP. Yet, this does not occur.

Muscle movement is the result of an incessant instantaneous breakdown and reconstitution of ATP. As fast as ATP fractures to free energy, it must be rebuilt. The methods that the muscles use to build up energy are aerobic (using oxygen) and anaerobic (not using oxygen).

The aerobic process takes place inside the mitochondria: the fuel for the aerobic process comes from glucose and fatty acids. Aerobic metabolism is by far the more efficient way to make ATP (39 moles of ATP from 1 mole of glucose), although it is not the faster.

Exercises to promote strengthening, conditioning, and pain control are prescribed regularly as part of the “medical armamentarium.”

The Journal of Musculoskeletal Medicine Vol 29 No 2

Tai Chi Improves Balance in Parkinson Disease

Recognizing Rheumatologic Aspects of Cocaine Abuse

Eosinophilic Fasciitis: A Difficult Diagnosis

Painless Groin Mass in an Active-Duty Soldier

Statins Reduce Cardiovascular Events in OA and RA

Lupus Disease Activity Decreases, but Damage Accumulates

Sleep Problems Increase Fibromyalgia Risk

How Muscle Works, and the Implications of Exercising

Understanding Function in RA: Importance and Measurement

Getting the Most Out of 3 Tesla MRI of the Spine

CASPAR Criteria for Psoriatic Arthritis Adapt Well for Retrospective Use

Low Pain Thresholds in RA Reflect “Fibromyalgic” Disease