JBJS | Instructional Course Lectures, The American Academy of Orthopaedic Surgeons

The Journal of Bone & Joint Surgery, Volume 78, Issue 7

Instructional Course Lecture | July 01, 1996

Instructional Course Lectures, The American Academy of Orthopaedic Surgeons - Simulators of Hand Infections*†

STEVEN E. KANN, M.D.‡; JOHN B. JACQUEMIN, M.D.‡; PETER J. STERN, M.D.‡, CINCINNATI, OHIO

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An Instructional Course Lecture, The American Academy of Orthopaedic Surgeons

The Journal of Bone & Joint Surgery. 1996; 78:1114-28

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Introduction

Inappropriate treatment of pathological processes that mimic infection can have catastrophic consequences. Prompt recognition may prevent unnecessary operative intervention and permit appropriate therapy. The purpose of this lecture is to acquaint the physician with infection simulators, to demonstrate how they can be confused with infection, and to give guidelines for treatment.

*Printed with permission of The American Academy of Orthopaedic Surgeons. This article will appear in Instructional Course Lectures, Volume 46, The American Academy of Orthopaedic Surgeons, Rosemont, Illinois, March 1997.

†No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. No funds were received in support of this study.

‡2800 Winslow Avenue, Suite 401, Cincinnati, Ohio 45206.

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Fig. 1. Radiograph of a hand with calcific tendinitis of the flexor carpi ulnaris. The calcific deposit (arrow) where the flexor carpi ulnaris inserts into the pisiform is best visualized on the oblique radiograph.

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Figs. 2-A and 2-B: Photographs of a hand that was bitten by a brown recluse spider. Fig. 2-A: Approximately two days after the bite, there was epidermolysis and a halo of erythema.

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Fig. 2-B Ultimately, there was full-thickness skin necrosis that necessitated debridement and skin-grafting.

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Fig. 3 Photograph of a pyogenic granuloma. The lesion developed following a laceration that was not closed operatively. It was excised, and the skin edges were approximated. It did not recur.

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Figs. 4-A, 4-B, and 4-C: Photographs of pyoderma gangrenosum of the hand in a patient who had ulcerative colitis. (Courtesy of John D. Wyrick, M.D.) Fig. 4-A: Hemorrhagic blisters had been present for three days.

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Fig. 4-B Dorsal and palmar photographs, made at ten days, revealed progression to digital necrosis. The patient died as a result of complications of the ulcerative colitis.

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Fig. 4-C Dorsal and palmar photographs, made at ten days, revealed progression to digital necrosis. The patient died as a result of complications of the ulcerative colitis.

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Figs. 5-A and 5-B: Metastatic carcinoma of the distal phalanx in a patient who was seen with what was thought to be a chronic paronychia. Fig. 5-A: Photograph of the hand, showing an ulcerating lesion of the thumb pulp.

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Fig. 5-B: Radiograph showing osteolysis of the tuft. Biopsy of a specimen showed metastatic squamous-cell carcinoma from the lung.

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Figs. 6-A, 6-B, and 6-C: A health-care professional who was referred for treatment of what she called spontaneously acquired non-healing wounds. Figs. 6-A and 6-B: Dorsal and palmar photographs of the hand.

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Figs. 6-A and 6-B: Dorsal and palmar photographs of the hand.

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Fig. 6-C: A radiograph of the hand revealed a piece of glass (arrows). The patient subsequently admitted to self-inflicted manipulation of the wounds.

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Fig. 7 Photograph showing a tophus of the metacarpophalangeal joint of the thumb, which had begun to drain. The patient had been referred for incision and drainage of a chronic infection of the joint.

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Fig. 8 Radiograph of the hand of a patient who had chronic gout. There are typical findings of asymmetrical joint involvement, periarticular erosions, and multiple soft-tissue tophi. The interphalangeal joint of the thumb demonstrates a classic periarticular erosion with an overhanging margin of bone.

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Fig. 9 Representative radiograph of a wrist with advanced calcium pyrophosphate deposition disease (pseudogout). There is prominent calcification within the triangular fibrocartilage complex and distal radio-ulnar joint, carpal and ulnar cysts, and advanced carpal collapse.

Acute Calcific Tendinitis

Acute calcific tendinitis may involve the hand and wrist as well as the shoulder, elbow, hip, or knee. Cohen, in 1924, was the first to describe calcium deposition in the hands and extremities²². The condition may be confused with infection because of the acute onset of symptoms; subtle radiographic findings; and physical findings of erythema, edema, severe pain, and occasionally fever^{18,30,57,102,140,143,165}.

In the hand and wrist, the condition most commonly presents during middle age, with a slight preponderance in women^19,165. Two cases in children have been reported^19,97. The etiology is unknown, but it has been theorized that a focal area of tissue necrosis caused by trauma or disease in conjunction with an alkaline environment permits calcium salts to precipitate¹⁹. The calcium deposits usually occur in or adjacent to ligaments and tendons^19,30,102.

The onset of symptoms is acute, with severe pain that is well localized over the tendon or ligament that contains the calcium deposit. The entire hand and wrist may be erythematous and swollen, with the specific region of the calcium deposit demonstrating point tenderness. The erythema and edema may extend proximally, mimicking cellulitis or lymphangitis, but there is no accompanying lymphadenopathy. The pain is often severe and is aggravated by both active and passive motion^114,115. There are no accompanying abnormalities in laboratory values, and the condition can be associated with a febrile response^19,56. Because the calcium deposits may be small and difficult to identify radiographically, it is important that radiographs be made centered on the region of maximum tenderness and in multiple projections to maximize visualization of the deposit. By region, the calcific deposits tend to be found in the ligaments of the phalanges, the intrinsic muscles of the palm, and the extensor or flexor tendons of the wrist. The most common site affected is the flexor carpi ulnaris tendon^19,20,102 near its insertion into the pisiform. In this location, the calcific deposit may be very small and easily overlooked on radiographs. A special radiographic view, made with the forearm in mid-supination, throws the pisiform into relief and demonstrates even a very small calcium deposit¹¹⁵ (Fig. 1). There is no relationship between the size of the calcium deposit and the magnitude of the pain, erythema, or swelling. The radiographic finding of a dense, amorphous, well circumscribed soft-tissue calcification confirms the diagnosis¹⁹.

Calcific tendinitis is a self-limited condition that resolves with or without treatment. Carroll et al. noted that the symptoms subsided in about three weeks without treatment¹⁹. However, there are reports in the literature of earlier resolution of the symptoms with intervention. With simple splinting, the time until relief of the symptoms was decreased to an average of nine days, and relief was obtained in an average of six days with injection of 1 per cent procainamide^57,102. Dilley and Tonkin found that relief occurred in an average of seven or eight days with the use of splints and anti-inflammatory medication³⁰. The symptomatic relief obtained from an injection of procainamide is the result of the release of tension within the deposit and the dissemination and absorption of the calcium salts¹¹⁵. The addition of a corticosteroid to the local anesthetic does not appear to enhance the efficacy of the injection^19,115. Of note, radiographic evidence of resolution lags behind clinical resolution of the symptoms by several weeks.

If the deposit is unusually large, then aspiration of the calcium salts may be performed. In rare cases in which the symptoms have been present for more than a month and the calcification appears very dense radiographically, an injection is not likely to be effective. In this situation, operative excision should be considered, and complete resolution of the symptoms can be anticipated within twenty-four to forty-eight hours¹⁹. Recurrence of the calcific tendinitis after resolution has occasionally been reported^{19,30,97,102,165}.

Bites of the Brown Recluse Spider (Loxoscelism)

The brown recluse spider, which at one time was indigenous to Central and South America, can now be found in all fifty United States. Most reported bites, however, occur in the southern and midwestern states. The local and systemic manifestations of the bite are variable, which complicates treatment.

This spider is able to live in a variety of conditions. It can tolerate extreme ranges in temperature, needs little food over extended periods, and can live inside or outside but prefers a dark, secluded habitat^132,166. It is approximately 0.5 to two inches (one to five centimeters) in length, and it can be identified by a violin-shaped mark on its cephalothorax and by six eyes in three pairs as opposed to eight eyes, as are found in most spiders¹⁶⁶.

In a classic bite scenario, the spider is living in clothing, bed sheets, or blankets that have been stored in a dark place and often bites when the victim is putting on clothes or rolling over in bed. The bite is perceived as a sharp sting or may go unnoticed. The spider often escapes, and the diagnosis is based solely on the history and the physical findings. The local reaction produces an urticarial rash that may progress to full-thickness skin necrosis¹³². The magnitude of tissue injury depends on the amount of venom injected and on the patient's immune status¹³². After several hours, a small hemorrhagic or erythematous blister develops that may be surrounded by a halo of ischemia. The erythema may spread rapidly and progress to a violaceous color. Snyder and Leonard stated: "A non healing ulcer with red, white, and blue phenomenon (erythema, ischemia, and cyanosis) is pathognomonic of a brown recluse spider bite."¹⁴⁹ During a period of twenty-four to forty-eight hours, the affected area may expand, resulting in full-thickness skin loss in an area as large as thirty centimeters in diameter⁴³ (Figs. 2-A and 2-B). If left untreated, the lesion forms an eschar, followed by ulceration in approximately fourteen days. Depending on its severity and size, the lesion can take weeks or months to heal.

Systemic reactions to the venom have also been reported and range from nausea, vomiting, fever, chills, and arthralgia to disseminated intravascular coagulation, convulsions, and massive hemolysis leading to renal failure and death^34,162.

The over-all approach to the treatment of loxoscelism is directed at three areas. First, the symptoms must be treated with antipyretics, sedatives, analgesics, and antipruritics. The second area of concern is the local wound. Treatment options include antihistamines, antibiotics, vasodilators, steroids (applied locally or systemically), operative excision, antivenin, hyperbaric oxygen, and oral administration of dapsone^{6,9,39,72,77,126}. Unfortunately, there have been few prospective evaluations of these therapies in animals or humans^125,126. The literature indicates that corticosteroids and early operative excision are not consistently beneficial, and early operative excision may be followed by delayed wound-healing and the formation of an abscess and scar^72,125,166. Rees et al., in a prospective study of humans, demonstrated that treatment with dapsone and antibiotics reduced the prevalence of secondary infections as well as the need for operative intervention¹²⁵. When an operation is necessary, it should be delayed until a mature eschar has formed and there is a need for skin-grafting. Dapsone should be used with caution; it has not been approved by the Food and Drug Administration for this application and, in rare instances, can cause hemolysis and agranulocytosis.

The treatment of the systemic symptoms and signs is supportive. All patients should have a baseline complete blood-cell count and urinalysis. Patients who have any systemic signs should be managed intensively with supportive therapy (intravenous administration of fluids and continuous monitoring of hemoglobin, renal electrolytes, platelet count, and coagulation factors) on an inpatient basis.

In conclusion, despite the variability in presentation and outcome associated with loxoscelism, close observation and treatment should be initiated to decrease the possibility of substantial local and systemic morbidity and, in rare circumstances, death.

Pyogenic Granuloma

The cause of pyogenic granuloma remains obscure. Its name is a misnomer, as it is not primarily a true infection. Many authors have thought that it is caused by chronic or repetitive irritation or trauma, with subsequent infection resulting in a proliferative, vascular response to an infectious organism of low virulence^94,161. However, other authors have believed that, because of the histological findings and the absence of trauma or irritation in some patients, it is an acquired vascular lesion, possibly with secondary infection. It has a strong association with pregnancy and the use of oral contraceptives. These lesions are found primarily in the oral mucosa, but they have been seen in the hand⁹⁴. Clinically, pyogenic granuloma must be differentiated from melanoma, particularly amelanotic melanoma. The primary and secondary small lesions may spread and can confuse the diagnosis⁹⁴. The lesion has also been described in two case reports as an intravenous pyogenic granuloma of the hand^23,29.

Grossly, the lesion is raised, red, and friable. On the hand, it is a papular lesion that bleeds easily and is usually found on the volar surface of the palm or digits (Fig. 3). Histological examination demonstrates both granulation tissue and inflammatory cells. The lesions range from one millimeter to one centimeter in diameter. They may develop spontaneously or follow an untreated laceration. There is an initial period of rapid growth, which may be alarming and may lead to suspicion of a cutaneous malignant tumor.

There are numerous methods of treatment, including radiation, cauterization with silver nitrate, electrocautery, laser therapy, curettage, tangential removal, and operative excision performed with or without a wide margin^{48,109,110,118,161}. All of these approaches may be followed by recurrence^4,38,141,159.

We recommend application of silver nitrate once or twice daily for ten days for the treatment of small lesions (less than 0.5 centimeter in diameter). For those that do not respond or for larger lesions, operative excision with use of magnification, removal of a small cuff of normal tissue, and meticulous hemostasis is effective. Treatment with antibiotics is usually unnecessary.

In the rare case of a pyogenic granuloma occurring on the hand during pregnancy or with the use of oral contraceptives, it is advisable to wait until the pregnancy is completed or for the patient to abstain from the use of the contraceptives for four to eight weeks. Any source of irritation, such as a ring, should be removed. Most lesions resolve spontaneously without operative intervention. In the event that the lesion is large or that a pregnant patient requests an excision, curettage or limited excision will suffice. Recurrence is uncommon⁹⁴.

Pyoderma Gangrenosum

Pyoderma gangrenosum is a rare, destructive, cutaneous lesion that presents as a painful, rapidly enlarging ulcer^{17,68,112,138}. It was first described by Brunstig et al.¹⁵, in 1930, and its etiology remains unclear. It is thought to be caused by a deficiency in the host immune system, and 80 per cent of patients who have pyoderma gangrenosum have a coexisting systemic disease¹²², most commonly ulcerative colitis. Fifty per cent of patients who have pyoderma gangrenosum have ulcerative colitis, but only 5 per cent of patients who have ulcerative colitis have pyoderma gangrenosum¹³⁸. Other associated diseases include Crohn disease, chronic active hepatitis, a carcinoid, diverticulosis, a myeloproliferative disorder, rheumatoid arthritis, diabetes mellitus, iron-deficiency anemia, and polyarteritis nodosa^{17,68,112,138,144}. However, 10 to 20 per cent of patients who have pyoderma gangrenosum have no evidence of systemic disease^{112,150,164,167}. The differential diagnosis includes erythema multiforme, necrotizing vasculitis, Sweet syndrome, bacterial pyoderma, blastomycosis, brown recluse spider bite, and necrobiosis lipoidica diabeticorum¹⁶⁷.

The lesions begin as red or black papules that arise acutely and are very painful. The lesion may also be associated with a fever. Within hours, pustules develop, spread rapidly, and undergo central necrosis (Fig. 4-A, 4-B, and 4-C). The border, which is irregular, raised, and violaceous, advances centrifugally at a rate of one to two centimeters a day.

The lesion is surrounded by an erythematous halo. In the initial stage, it is virtually indistinguishable from a pyogenic wound infection^111,167. If left untreated, most lesions eventually cease advancing and become indolent. Histological findings include a mixture of neutrophils and lymphocytes in small abscesses within the dermis.

The treatment of pyoderma gangrenosum should consist of local wound care (including changes of the dressing, application of topical sulfone compounds, and the use of a whirlpool), systemic treatment of the skin lesion, and the search for an associated systemic disease¹¹¹. Incision and drainage are contraindicated. Operative excision and closure of the wound can exacerbate the disease and leave a larger defect. Laurencin and Shoen described the excision of what was thought to be an infected ulcer⁸¹. The lesion recurred at the resection margin within twenty-four hours. This rapid reappearance of the lesion at the clear margins is one of the hallmarks of the disease¹⁴². Occasionally, the lesion may result in substantial necrosis, necessitating amputation.

Systemic use of steroids (sixty to eighty milligrams of prednisone a day) has been very successful in decreasing pain and resulting in the resolution of the lesion^{17,41,138,144,150}. If the use of corticosteroids is contraindicated because of the underlying disease (as with diabetes), then a sulfone such as orally administered dapsone¹⁴ or cyclosporin can be substituted⁴⁹.

Metastatic Lesions of the Hand

Metastatic lesions distal to the elbow are distinctively rare and nearly always occur in bone. Metastasis to soft tissue is extremely rare. A review of the world literature by Kerin, in 1983, identified only 156 metastatic tumors in the hand⁷⁶. Wu and Guise reported three metastatic lesions in the hand in 41,000 patients who had cancer¹⁶³. Despite the rarity of the lesion, awareness of its possibility is important to prevent a misdiagnosis of infection and, hence, a delay in proper treatment¹³¹. Amadio and Lombardi identified eighteen patients who had twenty-two metastatic lesions of the hand during a forty-three-year period⁵. The distal phalanx was the most common location, and the lung was the most common primary site. This is consistent with the literature, in which it was reported that more than 40 per cent of metastases to the hand (fifty-five of 129 in four series) arose from a primary lung tumor^44,76,93,101. The other sites of primary lesions are the breast, kidney, colon, thyroid, head and neck, and prostate.

The most common presenting symptom is continuous aching. The signs include erythema and swelling, with swelling in the phalanx presenting within six to eight weeks¹⁸ and metacarpal swelling presenting later because of the thicker soft-tissue envelope. If left untreated, the tumor may fungate, leading the unwary physician to suspect infection (Fig. 5-A). Radiographs typically reveal osteolysis within an associated soft-tissue mass (Fig. 5-B). A biopsy specimen should be taken for histological study and a culture specimen should be obtained to check for infection when any process destroys bone.

Most patients who have a metastatic lesion of the hand do not live for more than six months¹⁸. In one large review, the median duration of survival was less than five months⁵. Because of the poor prognosis, palliation is the primary goal for these patients. If the lesion is distal, conservative amputation provides the most rapid resolution of pain, obviates drainage from chronic wounds, and preserves maximum function of the hand. For more proximal lesions, local resection, with or without adjuvant radiation therapy, is effective in the short term and, again, preserves maximum function of the hand. Of the common primary tumors, carcinoma of the breast is most sensitive to radiation therapy.

Despite such a dismal prognosis, there have been cases in which wide excision of an isolated metastatic lesion resulted in a long-term disease-free interval⁵.

Foreign-Body Reaction

Injuries of the hand involving a foreign body are common. Usually the foreign body is removed; however, sometimes the patient is unaware of the penetration or the foreign body is not retrievable. Retained foreign bodies generate both acute and chronic inflammatory reactions, with the intensity of the reaction dependent on the type of material and the presence of any natural or synthetic toxins^{25,26,31,42,121}. Chronic inflammation leads to isolation of the foreign body by granulomatous tissue^25,42.

Most patients recall acute pain at the time of the initial injury. This may be followed by an asymptomatic period of weeks or months. There are several reports of previously asymptomatic patients being seen for an acute inflammatory reaction in the hand resulting from a foreign body that was deposited weeks or months earlier^51,100,127.

The symptoms of a foreign-body reaction are those of acute or chronic inflammation. When a foreign body is deposited in or near a joint, symptoms include the acute onset of pain, effusion of the joint, erythema, and a decreased range of motion. These findings simulate septic arthritis^{40,53,106,127}. A foreign body may also puncture or lie in proximity to tendon sheaths, causing aseptic inflammation, pain, and swelling^37,117,127. Erosion of bone in the hand after an initial diagnosis of osteomyelitis and failed treatment with antibiotics has often led to a biopsy or resection during which a sterile foreign body surrounded by a granuloma has been identified^8,51,117.

The diagnosis of a retained foreign body depends on clinical suspicion and imaging studies. Plain radiographs made in multiple projections are the first step. Russell et al. showed that adequate radiographs can demonstrate most foreign bodies¹³³. However, wood and plastic are difficult to demonstrate on plain radiographs¹³³, and computed tomography and magnetic resonance imaging may prove useful for the identification of such material^95,133. In the last several years, the use of ultrasound in the diagnosis of foreign bodies in the hand has gained popularity^64,69,82,83. This technique, while labor-intensive and operator-dependent, may supplant other techniques because it is less costly.

Treatment consists of operative removal. If there is secondary infection, culture of specimens and a short course of appropriate antibiotics are indicated. The complications of secondary infection, migration of the foreign body, and continued inflammation with damage to surrounding structures all militate against nonoperative treatment^{95,100,127,160}.

Factitious Diseases

Factitious disease of the hand presenting as an infection is unusual. Causes include factitious disorder and malingering⁷⁴. Factitious conditions may occur alone or in conjunction with another psychiatric illness such as conversion reaction⁷⁴. Regardless, factitious disorders are characterized by the patient controlling the signs and symptoms of the illness without being aware of his or her motive⁷⁴. In contrast, malingering is not strictly considered a mental illness since the patient consciously attempts to deceive others⁷⁴. The motive for secondary gain can be monetary or legal.

Grunert et al.⁵⁹ classified factitious disease of the hand into three categories on the basis of physical presentation: self-mutilation and manipulation of a wound (Fig. 6-A, 6-B, and 6-C), edema, and contractures. Some of the more common examples of self-mutilation include debridement, excoriation, and extension of wounds or operative incisions. In addition, new lesions or symptoms may develop along atypical paths of lymphatic drainage or in previously uninvolved areas^45,59,87,116. Patients who have factitious edema may have sharp demarcations or even ligature marks^124,148. Contractures of the hand may be simple or bizarre and cannot be explained on an anatomical basis. Frequently, these contractures involve muscles, nerves, or tendons that are unrelated to the described injury.

The diagnosis of factitious disease of the hand can be frustrating, time-consuming, and expensive. A high index of suspicion and thorough, non-confrontational evaluations are necessary. Several studies have stressed the importance of serial examinations to record the appearance of new wounds or a decrease in findings after the application of an occlusive dressing or cast^45,124. Phelps et al. applied fluorescein to the wound of one patient and then applied an occlusive dressing¹¹⁶. Subsequent examination with a Wood lamp detected fluorescence under the nails of the uninjured hand and confirmed manipulation of the wound¹¹⁶. Phelps et al. recommended this procedure for detection of factitious disease. In our experience, culture of specimens from self-inflicted wounds often reveals several different types of organisms, including ones such as Enterobacter cloacae and Escherichia coli that are not usually associated with infections in the hand.

After the physician has determined that an injury of the hand is factitious, the patient may be managed non-operatively. A non-confrontational explanation of the facts is recommended, as many authors have described severe emotional and psychiatric consequences of doctor-patient confrontations^3,32. Referral to a psychiatric professional is necessary to diagnose and treat underlying disorders. The prognosis for patients diagnosed with factitious disease is mixed. Grunert et al.⁵⁹ found that angry or hostile patients who manipulated their wounds were especially prone to have a poor result.

Gout

Gout, in our experience, is among the most common simulators of hand infection. Any man who is more than forty years old and is seen for the acute onset of soft-tissue, tenosynovial, or synovial swelling should be carefully questioned regarding a history of hyperuricemia.

Gout is the most common of the crystalline deposition diseases, with descriptions dating back to Hippocrates². Its pathogenesis begins with hyperuricemia and the saturation of a joint space, tendon sheath, or bursa with monosodium urate crystals^75,154. In some individuals, urate crystallizes out of solution and causes an inflammatory reaction in the involved tissue. While the exact triggering mechanism is unknown, many factors, such as temperature, age, previous damage to the tissue, and heredity, may play a role^73,154.

Recording a history aids in the diagnosis of gout, with most patients (1802 of 1900 in one study¹⁶⁹) being middle-aged or elderly men. Women who are affected are almost exclusively postmenopausal, as estrogen promotes the excretion of urate^75,84,154. Indeed, the onset in premenopausal women necessitates additional investigation to check for enzyme defects or renal disease. Obesity and a high alcohol intake are also frequently associated with gout^75,154. Medications, such as thiazide diuretics or antimetabolites, can cause hyperuricemia and may precipitate an acute flare-up of gout^75,92,130.

Questioning about a history of joint pain or a family history of gout is warranted. Previous episodes of monarthritis, particularly in the metatarsophalangeal joint of the great toe, the midtarsal joint, or the knee, that developed quickly and subsided should raise suspicion of gout⁷⁵. A history of chronic or severe gout in the lower extremity increases the likelihood of involvement of an upper extremity⁷⁵. A family history of gout may be found in as many as 40 per cent of patients^55,75,169.

Gout is often confused with an infectious process as gout attacks may occur after an operation, infection, trauma, or illness^{1,54,67,73,89,99,129,130,151,156}. A recent study of hospitalized patients who had crystal synovitis found that symptoms had developed in 75 per cent after they were admitted for non-musculoskeletal health problems⁶⁷. Gouty arthritis may be precipitated even after minor trauma^80,130,151. Postoperative attacks of gout mimicking infection of the treated hand have been reported in patients who have had a carpal tunnel release^54,73.

Physical examination of the wrist and hand yields similar findings in gout and infectious arthritis or tenosynovitis^54,73,75,130. Gout presents with acute swelling, erythema, and pain that is exacerbated by active or passive motion. Patients with these symptoms may also be febrile^99,105. Tophi are not present in new-onset attacks, but they should be sought elsewhere as evidence of chronic disease^86,152 (Fig. 7). Aspiration with crystalline analysis is helpful for establishing a diagnosis and thereby avoiding operative intervention.

Laboratory studies are non-specific. Both gout and infection may yield elevated erythrocyte-sedimentation rates and leukocyte counts^75,119,153. Serum levels of uric acid, while helpful, are not diagnostic and are normal in 23 to 46 per cent of patients^61,75,120.

Analysis of the synovial fluid is the primary means of diagnosing gout^75,86,153. Even a few milliliters of synovial fluid can be analyzed for urate crystals⁷⁵. Detection of negatively birefringent crystals with a polarizing microscope confirms the diagnosis^75,153. Determination of glucose, leukocyte, and protein levels in the synovial fluid may be helpful but is frequently non-specific in the differentiation of infection from gout^75,129,153. Gram stains and cultures should be performed for all patients, as gout and infection may occur together^7,147.

Radiographs are useful in the diagnosis of chronic, but not acute, gout. Radiographic examination of patients with new acute-onset gout reveals only soft-tissue swelling or effusion of the joint. In chronic gout, tophaceous deposits (which appear as soft-tissue masses) may be detected. Additionally, well marginated erosions of bone may occur. These are typically round or oval, are oriented along the long axis of the bone, and may be intra-articular, periarticular, or at a distance from the joint. They may be large (more than five millimeters in diameter) and can be surrounded by a sclerotic border. In many patients, the erosion is partially surrounded by an overhanging margin of bone. In the hand and wrist, any joint may be involved. Preservation of the joint space (until late in the disease) and asymmetrical joint involvement help to distinguish gout from rheumatoid arthritis¹²⁸ (Fig. 8).

Medical treatment of inflammation and pain is the first priority in the management of patients who have acute gout^35,157. Colchicine and high-dose non-steroidal anti-inflammatory drugs are the first line of treatment^75,151. The recommended dosage of colchicine for acute attacks is 0.6 milligram every two hours until the patient has relief; until intestinal symptoms, such as nausea or diarrhea, develop; or until a maximum dose of six milligrams has been given⁷⁵. Dosages of anti-inflammatory medications vary. Indomethacin, one widely used drug, may be given in an initial dose of fifty to seventy-five milligrams and then in a dosage of twenty-five to fifty milligrams three or four times a day. For patients in whom colchicine and non-steroidal anti-inflammatory medications are contraindicated, systemic or intra-articular administration of corticosteroids may be equally effective^35,75,151. With proper treatment, most patients respond within twenty-four to forty-eight hours⁸⁶. Hypouricemic agents, such as probenecid or allopurinol, should not be added or adjusted during an acute attack of gout as they may exacerbate the attack^75,153. Operative treatment is not indicated for acute gout¹².

Pseudogout

Intrasynovial deposition of calcium pyrophosphate crystals was discovered in 1961, during studies of patients who were believed to have gout^79,91. Since then, similar crystalline deposition has been found in tendons, ligaments, and joint cartilage. Appropriately termed calcium pyrophosphate deposition disease, this clinical illness is also known as pseudogout. Radiographic evidence of deposition in hyaline cartilage or fibrocartilage (Fig. 9) has led to the term chondrocalcinosis.

A pathological study demonstrated calcium pyrophosphate crystal deposits in 5 per cent (thirty-two) of 598 cadaver specimens of patients who were an average of seventy-two years old at the time of death⁸⁹. However, the prevalence of clinically symptomatic patients is much lower. Most studies have shown the prevalence of symptoms to be half that associated with gout, or about one in 1000 patients¹⁰⁷.

A patient history aids in the diagnosis. Most symptomatic patients are in at least the seventh decade of life. Many can describe previous episodes of pain and weakness in the affected joint^89,107. Pseudogout may also be associated with metabolic diseases such as hemochromatosis, gout, hyperparathyroidism, and hypothyroidism^70,107. As is the case for gout, an operation, trauma, or severe illness may precipitate acute attacks of pseudogout^36,63,96,158. Occurrence in an ill patient may particularly raise the suspicion of an infectious process.

Pseudogout most commonly affects the knee. The wrist is the most common location in the upper extremity, with the lesion occurring less frequently in the metacarpophalangeal joints. Symmetrical involvement of joints is the rule; however, attacks are often unilateral.

Physical examination of the affected hand or wrist reveals the joint to be inflamed, with a mild or moderate effusion and a decreased range of motion. A pyarthrosis may be suspected on the basis of physical findings, but other methods of evaluation, including plain radiographs and arthrocentesis, aid in establishing the correct diagnosis. Pain on the ulnar side of the wrist may be particularly prominent since the triangular fibrocartilage complex is commonly involved. Radiographic evidence of chondrocalcinosis in the triangular fibrocartilage complex in a patient who has acute pain on the ulnar side of the wrist as well as an effusion is highly consistent with pseudogout. Attacks usually last about one week and may be accompanied by a low-grade fever. Acute compression of the median nerve, similar to that seen with infection of the carpal tunnel, may occur as a result of deposition of calcium pyrophosphate^21,52,98,123.

Screening for deposition of calcium pyrophosphate can be done with radiographs of the knees, hips, pubic symphysis, and wrists^47,107,139. Additional study is unlikely to yield positive results if these areas are devoid of calcification. A presumptive radiographic diagnosis of pseudogout may be made on the basis of punctate or linear densities in articular or fibrocartilaginous tissues.

The definitive diagnosis is based on analysis of the synovial fluid. Calcium pyrophosphate crystals are usually irregular or rhomboid in shape, although needle-shaped crystals, as in gout, may be encountered. Unlike the negatively birefringent gouty crystals, the crystals in pseudogout are positively birefringent when viewed under a polarizing microscope.

Calcium pyrophosphate crystals cannot be removed from tissues. Treatment of associated diseases also has no proved effect on the progression of crystal deposition¹⁰⁷. Symptomatic attacks in the hand may be treated with colchicine or non-steroidal medications, such as indomethacin. Injection of corticosteroids has proved useful in selected patients^70,90. For lesions presenting as carpal tunnel syndrome, operative release is the treatment of choice²¹.

Rheumatoid Arthritis

Rheumatoid arthritis, juvenile rheumatoid arthritis, and the seronegative spondyloarthropathies have many pathological characteristics in common, including the ability to cause chronic progressive destruction of the hand and wrist. Confusion of an infectious condition with one of these inflammatory disorders is uncommon. However, when patients are seen because of the acute onset of monarticular inflammation or when the usual associated signs and symptoms are lacking, the specific diagnosis may be more difficult. Of the many autoimmune-related diseases, only rheumatoid arthritis and juvenile rheumatoid arthritis tend to present in this fashion.

While patients typically describe the insidious development of painful swollen joints in a symmetrical polyarticular fashion, confusion with an infectious process may occur when symptoms develop more acutely and in fewer joints. Acute onset has been found in 8 to 15 per cent of patients⁶⁵. The acute onset of rheumatoid arthritis is especially common in elderly patients^24,28. In addition, many authors have noted monarthritis, usually of the knee or wrist, as the initial manifestation of rheumatoid arthritis^27,155. Episodic attacks of monarticular arthritis, with periods of complete remission, also have been described. These attacks, termed palindromic arthritis, evolve into rheumatoid arthritis in approximately 33 per cent of patients (218 of 653 in two studies^60,136).

Complicating the diagnosis of rheumatoid arthritis is the potential coexistence of septic arthritis. Patients who have rheumatoid arthritis are more prone to joint infections¹⁰³. Reasons for this may include the local and systemic effects of rheumatoid arthritis, the presence of other illnesses, or treatment with immunosuppressive medications¹⁰³. Infection of the same joint may recur in as many as one-third of patients, and polyarticular joint infections develop in many patients. In order to preserve function and to prevent recurrence, such infections necessitate more intensive treatment than do similar infections in otherwise healthy patients^{11,50,103,104}.

In rheumatoid arthritis, physical examination of the digits reveals fusiform swelling, warmth, and a decreased range of motion of involved joints. Swelling on the volar aspect of the digits indicates inflammation of the flexor tendon sheaths. While involvement of the distal interphalangeal joint is less common, it does not exclude the diagnosis of rheumatoid arthritis^62,71. Distinction from an infectious process may be impossible on the basis of physical examination alone.

Laboratory studies are frequently not helpful in the early diagnosis of rheumatoid arthritis. Initial laboratory analysis often reveals non-specific elevations of the leukocyte count, the erythrocyte sedimentation rate, and the level of C-reactive protein. A positive rheumatoid factor is valuable as an indication, as 85 per cent of patients with rheumatoid arthritis have a positive test for rheumatoid factor¹⁴⁵. However, the rheumatoid factor may remain negative for one to two months after the onset of the disease¹³⁶. Analysis of the synovial fluid for bacteria and crystals is negative. Also, the total white-blood-cell count in the synovial fluid is lower with rheumatoid arthritis (usually 2000 to 75,000 cells per cubic millimeter [2 X 10⁹ to 75 X 10⁹ per liter]) than with septic arthritis (often more than 100,000 cells per cubic millimeter [100 X 10⁹ per liter])¹³⁷.

Radiographs are usually not useful in the diagnosis of new-onset rheumatoid arthritis and reveal only evidence of soft-tissue swelling¹²⁸.

Effective treatment of rheumatoid arthritis depends on interruption of the complex inflammatory process. Aspirin and non-steroidal medications are first-line treatments. The trial of an agent at maximum dosage for two weeks appears to be the most accurate way to assess the efficacy of the drug^13,33. Other medications, such as gold compounds, antimalarials, cytotoxic agents, or low-dose corticosteroids, are generally reserved for chronic progressive disease^46,56,78,88. An operation is not indicated in the treatment of acute rheumatoid arthritis.

Juvenile rheumatoid arthritis, like rheumatoid arthritis, is an autoimmune disease of unknown etiology. Unlike rheumatoid arthritis, juvenile rheumatoid arthritis has several distinct subtypes. In particular, monarticular juvenile rheumatoid arthritis may be confused initially with infection and occurs in 10 per cent (thirty-three of 316) to 31 per cent (forty of 130) of patients^16,20. Pauciarticular arthritis or polyarthritis may subsequently develop in children who initially have monarticular disease. However, there is no way to predict which children are at risk for more widespread disease¹⁰. Affected joints include the knees, ankles, elbows, and wrists^10,58,134. The hips and small joints of the hand are often spared. Systemic signs and symptoms such as fever are rarely present.

The diagnosis of juvenile rheumatoid arthritis is frequently one of exclusion. Aspiration of the joint, with gram-staining and culture of synovial fluid, should be done for all patients to rule out infection. Serum blood tests for rheumatoid factor are rarely positive; however, antinuclear antibodies may be positive in as many as 85 per cent of patients^113,135. Radiographic evaluation frequently reveals only soft-tissue swelling.

As it does with rheumatoid arthritis, treatment centers around the reduction of inflammation of the involved joints. Aspirin and non-steroidal medications are used to decrease inflammation, although not all antiinflammatory drugs are approved for use in children¹⁴⁶. Parents should be warned of the dangers of Reye syndrome in association with treatment with aspirin and should be told to briefly discontinue the use of aspirin during and after viral infections. Administration of corticosteroids systemically or by injection is contraindicated in most patients because of the potential for retarded skeletal growth^85,108,146. Children who have monarticular or oligoarticular arthritis should be evaluated regularly by an ophthalmologist because of the occurrence of uveitis^16,66,146.

In summary, despite the availability of an ever-enlarging technological armamentarium, the patient's history and physical examination remain pivotal with regard to arousing suspicion of an infection simulator. Once suspicion is raised, the diagnosis can usually be confirmed with simple laboratory tests or plain radiographs. Failure to include infection simulators in the differential diagnosis may lead to inappropriate medical or operative treatment and may compromise the clinical outcome.

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