The multisystem effects caused by Borrelia burgdorferi in Lyme disease are multiple, varied, and unpredictable. In some patients, the full extent of the infection consists of a stage I acute systemic viral-like illness. Stage II primarily involves the cardiovascular system (myocarditis) and/or the central nervous system (CNS) (meningoencephalitis, polyradiculitis). More inflammatory cells are found in the heart and nervous system structures during this intermediate stage than are found in any tissues involved during stage I. Stage III is characterized by peripheral neuropathy and CNS disorders such as dementia or transverse myelitis and arthritis and synovitis of large joints such as the knee. Chronic Lyme disease is also associated with multiple and seemingly unrelated cutaneous manifestations such as acrodermatitis chronica atrophicans, sclerodermoid-like reactions, lichen sclerosus et atrophicus, subcuticular fibrous nodules, eosinophilic fasciitis-like lesions of the extremities, and, possibly, granuloma annulare. With care, spirochetes can be recovered or demonstrated by silver staining in most of the above lesions. Spirochetes have yet to be seen in the tissues of autonomic ganglia or peripheral nerves.