Hal J. Mitnick

Drug-induced arthritic and connective tissue disorders.

OBJECTIVES All pharmacologic agents have the potential for both benefit and toxicity. Among the more interesting and important adverse consequences of drug therapy are a range of joint and connective tissue complaints that may mimic or reproduce primary rheumatologic diseases. In this article, we review the literature on commonly used drugs reported to induce arthritis and/or connective tissue-based diseases. We assess the strength of the reported associations, discuss diagnostic features and treatment implications, and consider possible mechanisms for drug-induced genesis of rheumatic conditions. METHODS We reviewed the Medline database from 1987 to 2006 to identify drug-induced arthritic and connective-tissue disease syndromes, utilizing 48 search terms. A qualitative review was performed after the articles were abstracted and the relevant information was organized. RESULTS Three hundred fifty-seven articles of possible relevance were identified. Two hundred eleven publications were included in the final analysis (case series and reports, clinical trials, and reviews). Many drugs were identified as mimicking existing rheumatic conditions, including both well-established small molecules (eg, sulfasalazine) and recently introduced biologic agents (eg, antitumor necrosis factor agents). The most commonly reported drug-induced rheumatic conditions were lupus-like syndromes. Arthritis and vasculitis were also often reported. CONCLUSIONS Drug-induced rheumatic syndromes are manifold and offer the clinician an opportunity to define an illness that may remit with discontinuation of the offending agent. Early diagnosis and withdrawal of the drug may prevent unnecessary morbidity and disability.

Drugs Causing Muscle Disease

Many drugs can cause myopathies, and such myopathies may range widely from asymptomatic elevations in the serum creatine phosphokinase levels to severe myalgias, cramps, exercise intolerance, muscle weakness, and even rhabdomyolysis. In this article, some of the commonly used drugs that may induce myopathies, as well as the clinical phenotypes, diagnosis, and management of these syndromes are reviewed.

Headaches Related to Rheumatologic Disease

Headaches are a common, but under-recognized and understudied symptom in the context of the rheumatic diseases. They can result from intracranial pathology, such as parenchymal and meningeal inflammation, thrombosis, space-occupying lesions, and more. Inflammation, irritation, or degeneration of anatomically related structures such as the eyes, neck, and sinuses can equally cause headaches. In addition, patients with rheumatologic disorders have the same tendencies as the general population to develop primary headaches. While the latter are benign in nature, and generally require only symptomatic relief, the former type of headaches may signal disease manifestation, progression, or complication. Thus, familiarity with common and uncommon headache syndromes related to rheumatologic disorders as well as with their possible underlying disease processes and mechanisms is important. This will help to successfully develop an effective approach toward the evaluation of patients presenting with headaches in a rheumatologic context, and, ultimately, diagnose and treat potentially severe underlying disease.

Lyme disease presenting as ruptured synovial cysts.

To the Editor: We have read with interest the letter to the editor from Bhambhani et al. and would like to present 2 additional cases of Lyme disease presenting as a ruptured synovial cyst that are pertinent to the report. Furthermore, these cases emphasize some of the suggestions these authors made regarding diagnosis of this disease. Periarticular synovial cysts of the knee (e.g., Baker cyst) with or without rupture are common in the general population. A Baker cyst may represent a true cyst but more commonly results from the posterior herniation of a tense knee effusion. They are typically associated with rheumatoid arthritis, osteoarthritis (OA), meniscal tears, and synovitis of diverse etiologies. Ultimately any cause of synovitis could be associated with rupture. Synovial effusion, while common in Lyme arthritis has rarely been reported in association with cyst rupture. We describe 2 cases of Lyme disease presenting with cyst rupture and pseudo-thrombophlebitis. In both cases, delay in diagnosis led to inappropriate therapy and morbidity. Case No. 1. Nine months prior to admission (PTA), a 54-year-old Caucasian male noted acute onset of pain in the right knee with calf swelling. Magnetic resonance imaging (MRI) revealed a meniscal tear with ruptured Baker cyst. Treatment with valdecoxib and physical therapy led to improvement. Two months PTA, he developed similar symptoms in the left knee. MRI again revealed meniscal tear and a ruptured Baker cyst. He was treated accordingly. Six days PTA, he developed acute onset pain and swelling in the right knee and calf. He denied tick bite and had no other manifestations of Lyme disease. On admission, the right knee revealed moderate erythema, warmth, and swelling associated with popliteal fullness extending to the right calf. Duplex ultrasound (US) showed a noncompressible mass at the right popliteal fossa without venous obstruction. Arthrocentesis of the right knee revealed inflammatory synovial fluid, which tested positive for Borrelia burgdorferi by polymerase chain reaction (PCR). Lyme enzyme-linked immunosorbent assay and Western blot were positive in serum. Ceftriaxone 2g intravenously (IV) every 24 hours was administered for 4 weeks leading to resolution. He had no recurrence after 6 months. Case No. 2. Six years PTA a 59-year-old Caucasian male developed erythema chronicum migrans (EM) and received 1 week of antibiotic. In the 2 years PTA, he developed 4 attacks of recurrent left knee pain and swelling with mild fever. Episodes were treated with NSAID and resolved. After the third attack, a diagnosis of OA was made based upon MRI findings of patellofemoral OA with knee effusion. Three weeks PTA, he developed gradual onset right knee and ankle pain and swelling. Ibuprofen provided partial resolution. One week PTA, pain and swelling spread from the right knee to the right thigh and upper calf. Four days before, he developed a fever and was hospitalized. MRI revealed large effusion under tension with marked distension of the right suprapatella bursa and rupturd popliteal cyst (Fig. 1). Serum enzyme-linked immunosorbent assay and Western blot were positive for Lyme disease. Synovial fluid PCR for B. burgdorferi was negative from the right knee but positive from synovitis which developed in the left knee a few days later. Ceftriaxone 2g IV every 24 hours was administered for 4 weeks with resolution. He had no recurrence after 6 months. We have described 2 patients with synovial cyst rupture due to Lyme arthritis, both confirmed by B. burgdorferi DNA in synovial fluid using PCR. Each was successfully treated with IV antibiotic therapy leading to resolution of inflammatory events. These cases are noteworthy as they reveal a treatable disease that was mistakenly assumed to be due to coexistent OA with meniscal pathology. Considering the prevalence of Lyme disease, OA and meniscal tears, we assume other cases of Lyme disease leading to synovial cyst formation have been overlooked in endemic areas. Late articular manifestations of Lyme disease are common in patients with inapparent infection or untreated EM. This was demonstrated in a study of 55 patients with nontreated EM where 80% of patients developed an articular manifestation over a mean period of 6 years. In areas endemic for Lyme disease, adult patients with OA, meniscal tears, and synovial cysts should be tested for Lyme disease with serologies and synovial fluid PCR. FIGURE 1. Fat-suppressed T2-weighted magnetic resonance imaging of right leg in case 2. The left panel demonstrates a large effusion under tension with marked distension of the right suprapatella bursa (arrow). Right panel demonstrates diffuse fluid between fascial planes behind the left knee from ruptured popliteal cyst (arrowhead).