A45-year-old male presents to the primary care office with a chief complaint of generalized musculoskeletal pain for a four months. He says it has been getting worse over the last month to a month in a half in the form of brief attacks of joint pain and mild swelling. The patient adds that he had a low-grade fever about a week ago.

The musculoskeletal pain began several weeks after the patient returned from a weekend camping trip to the eastern shore of Maryland. He had multiple insect bites during this camping trip. The patient describes the pain as a stiff, aching “arthritis-like pain in multiple joints of the body.” He cites pain in his left and right hands, right knee, left and right elbows, and left hip. He says the pain began gradually and “seems to move around.”



He states the pain is worse when he sits for long periods of time. The patient says his joints seem to become “more stiff” during the “attacks,” which could last for one to two weeks at a time. He has tried many over-the-counter remedies including Advil, Aleve, Tylenol and glucosamine chondroitin with no significant relief. The pain and stiffness has gotten to a point where the patient has begun to miss additional days of work and is often unable to move around in his job working as an admissions recruiter for a local university. The patient has not previously sought medical attention for this problem.

He denies any musculoskeletal trauma or previous injury, fever, chills, weight loss, change in appetite, rash, throat pain, neurological symptoms, bowel or bladder changes. His past medical history is unremarkable and he has no significant surgical history. The family history is significant for hypertension and hyperlipidemia.
The physical examination reveals a well-developed and well-nourished middle-aged male in no apparent distress. His vital signs include a sitting blood pressure of 126/80, a respiratory rate of 16, and a heart rate of 86 with regular rate and rhythm. He weighs approximately 198 pounds with clothes and is 5’10” without shoes.

The dermatological exam reveals a mildly erythematous macular rash on the left lateral posterior trunk that measures 12 cm in diameter. There are several small annular macular lesions on the posterior aspect of the left and right lower extremity. The hair distribution is even, the patient’s skin color is without cyanosis and his skin texture is smooth with some dryness and rapid turgor.

The patient’s heart exam shows no lifts, heaves, thrills, visible point of maximal impact (PMI), murmurs, gallops, ectopy, and S1 and S2 are present with no S3 or S4.

His lung exam reveals no bony deformity and no use of accessory muscles. His lungs are resonant to percussion and one can hear vesicular lung sounds on auscultation with no wheezing, crackles, rales or rhonchi on inspiration or expiration.

The patient’s neurological exam shows intact cranial nerves and no signs of atrophy. We tested muscle strength against active and passive ROM. He has an upper muscle strength of +4 bilaterally with some mild weakness on extension and lower muscle strength reveals +3 bilaterally. The patient is able to perform rapidly alternating movements. He has no neural deficits with light touch or superficial pain, and sensation is equal bilaterally.

The physical examination of the musculoskeletal system reveals multiple areas of point tenderness over the right knee and below the elbow joints. There is also decreased flexibility and ROM of the left hip, right knee, the right ankle and below the elbows. Deep tendon reflexes are equal bilaterally.
Which of the following is the likely diagnosis?

A. Lyme disease
B. Systemic sclerosis
C. Systemic lupus erythematosus
D. Degenerative joint disease

Pertinent Pearls On
The Differential Diagnosis

A. The diagnosis of Lyme disease arthritis is correct. Lyme disease is caused by the Borrelia burgdorferi, a spirochete which is a vector from the Ixodes tick species. Small mammals and deer often serve as the principal hosts of the tick. Lyme disease is a multi-system disease that progresses gradually and can affect the heart, lungs, nervous and musculoskeletal systems.

It occurs in three different stages. Stage one is characterized by a macular dermatitis known as erythema migrans that develops at the site of the tick bite. This may be absent in approximately 25 percent of cases. Stage one Lyme disease may resolve spontaneously in three to four weeks.

After several days to weeks, the disease may progress to the second stage. In this stage, the organism is disseminated to other organ systems and causes illness, fever, fatigue, arthralgias, adenopathy, annular skin lesions and meningitis. In addition, one may also diagnose cranial peripheral neuritis, peripheral neuropathies and facial nerve palsy that may be unilateral or bilateral. There also may be oligoarthritis in multiple joints with migratory pain in bursae, joints, tendons, muscles or bones usually without joint swelling. Pain of this type may last hours, days or even longer.

Stage three is characterized by persistent infection and is present months after the infection. In this stage, there is persistent oligoarthritis affecting large and small joints. There are times in which there may be intermittent attacks of joint paint that can become chronic and eventually lead to the erosion of cartilage and bone. Additional manifestations during this stage can include myocarditis, encephalopathy, axonal polyneuropathy and leukoencephalopathy.

The patient started to experience generalized musculoskeletal pain several weeks after a camping trip. He noted that he had multiple insect bites during the trip.

While one primarily diagnoses the disease via the clinical history, clinicians may obtain serologic confirmation by using the enzyme-linked immunosorbent assay (ELISA) as well as confirmation via Western blotting. However, keep in mind that serologic testing does not distinguish between active and inactive infection. One may obtain cultures on the skin lesions of patients with the disease. In cases of Lyme arthritis, detection of spirochetal DNA via polymerase chain reaction may serve as an alternative for culture in cases of Lyme arthritis.

In this case, the patient presented with joint pain, annular lesions, fever, migrating joint pain and had a history of outdoor recreational activity in an area in which there are many cases of Lyme disease. Additionally, the timeframe of the complaints leads the practitioner to consider that the disease has progressed to the latter stages in which there is significant joint involvement with intermittent exacerbations of oligoarthritis. Also, the decrease in muscle strength may be indicative of a developing peripheral neuropathy.

First-line treatment for Lyme disease is doxycycline 100mg po BID for 10 to 21 days in the initial stage of illness. Alternative treatments include amoxicillin 500mg TID for 10 to 21 days, cefuroxime 500mg po BID for 21 days and clarithromycin 500mg po BID for 21 days.

B. Systemic sclerosis (scleroderma) is not the correct answer. The etiology of scleroderma is unknown but possible causes may include autoimmunity, fibroblast dysregulation, graft-versus-host disease from fetal lymphocytes retained in the maternal circulation, and occupational exposure to silica. People usually have symptoms in their 30s to 50s, and women are affected two to three times as frequently as men. Polyarthralgia and Raynaud’s phenomenon are the initial complaints in 60 to 70 percent of patients. Clinicians generally recognize two forms of systemic sclerosis. Limited sclerosis occurs among 80 percent of patients and diffuse sclerosis occurs in 20 percent of patients.

Scleroderma is characterized by thickening and fibrosis of skin (scleroderma) and internal organs (heart, lungs, kidneys and gastrointestinal tract.) The skin thickening is due to accumulation of collagen in lower dermis. The fixation and immobility of skin is caused by replacement of subcutaneous tissue with fibrous band. Patients with diffuse or generalized systemic sclerosis are at risk for rapidly progressing, widespread skin involvement and early development of a complement of internal organ abnormalities.

When patients have slowly progressive skin changes, these changes are restricted to the fingers, hands and face. These patients may also have an extended course of illness before the visceral abnormalities. This group has CREST syndrome (subcutaneous calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly and telangiectasia). The laboratory findings associated with systemic sclerosis include mild anemia, positive antinuclear antibodies, and proteinuria and cylindruia in association with renal involvement. The sclerodoma antibody (SCL-70) is present in one-third of patients with diffuse systemic sclerosis and in 20 percent of those with CREST syndrome. Treatment is symptomatic and supportive.

C. Systemic lupus erythematosus (SLE) is not the correct answer. Systemic lupus erythematosus is a chronic inflammatory autoimmune disease of unknown origin that affects multiple organs. It affects women more that men. The prevailing thinking is that clinical manifestations such as inflammation, tissue damage and effects on multiple organs are secondary to the trapping of antigen-antibody complexes in capillaries of visceral structures. The course and severity of SLE varies widely to include fever, anorexia, malaise, weight loss, skin lesions, oral ulcers, eye pain and arthritic pain. Additionally, the clinical features may include a malar (butterfly) rash, discoid rash, photosensitivity, arthritis, serositis, pleuritis, pericarditis and nephritis.

Ms. Harrison is an instructor within the Drexel Hahnemann Physician Assistant Program at Drexel University in Philadelphia.

Joint symptoms are common and are often the earliest manifestation. The joints commonly involved are the proximal interphalangeal (PIP) joints, the metacarpophalangeal (MCP) joints, carpal bones, knees and ankles. The diagnostic studies associated with SLE include: positive antinuclear antibodies (sensitive but not specific for SLE); positive serum rheumatoid factor; and positive antibodies to double-stranded deoxyribonucleic acid (anti-dsDNA) antibody and to anti-Smith (anti-Sm) (specific, but not sensitive to SLE).

The treatment of SLE includes avoidance of ultraviolet light, early intervention when infection occurs, and the avoidance of physical and emotional stress. Pharmacological treatment includes nonsteroidal inflammatory medication, corticosteroids and antimalarials (hydroxychloroquine).

D. Degenerative joint disease (osteoarthritis) is not the correct answer. It is the most common form of arthritis as it affects 85 percent of adults 65 years of age and older. This arthropathy is characterized by cartilage degeneration and bone hypertrophy at the articular margins.

Dr. Auth is the Clinical Editor of Diagnostic Dilemmas. He is also a physician assistant and is the Director of the Drexel Hahnemann Physician Assistant Program at Drexel University in Philadelphia.

Degenerative joint disease (DJD) can be primary or secondary. Primary DJD commonly affects some or all of the following terminal interphalangeal joints (Heberden’s nodes); proximal interphalangeal joints (Bouchard’s nodes); as well as the wrist, hip, knee, thumb, big toe and cervical/lumbar spine. Secondary DJD may occur in any joint as a sequela to articular injury resulting from either intraarticular or extraarticular causes. The onset of symptoms are insidious and seldom last more than 15 minutes.

Patients with either primary or seconday DJD may also develop pain with motion of the affected joint. Indeed, these patients usually have pain after exercise or use of the joint. Radiographic studies may reveal narrowing of the joint space, sharpened articular margins, ostephyte formation and lipping of marginal bone.
Possible treatment options include weight reduction, supportive measures (activity modification, cane), analgesic and antiinflammatory medications, and surgical procedures (arthroscopic debridement, total joint replacement).