Raphael B. Stricker

Clinical and immunologic evaluation of HIV-infected patients treated with dinitrochlorobenzene

BACKGROUND Promotion of cell-mediated immunity appears to be an important goal in the control of HIV infection. Topical dinitrochlorobenzene (DNCB) stimulates systemic cell-mediated immunity via the induction of cutaneous delayed-type hypersensitivity. OBJECTIVE Our goal was to evaluate the clinical and immunologic effects of chronic DNCB application in a group of 24 HIV-infected patients. METHODS We observed the patients for a mean of 28 months (range, 14 to 44 months). Of the 24 patients, 13 continued weekly DNCB application throughout the study (the compliant group), and 11 discontinued DNCB use after a mean of 10.9 months (the noncompliant group). RESULTS Two of the 13 compliant patients progressed to AIDS; none of these patients died. In contrast, AIDS developed in 5 of the 11 noncompliant patients and four of these patients died. Analysis of lymphocyte subsets revealed significant increases in natural killer cells and activated/cytotoxic CD8 T-cell subsets in the compliant group. In contrast, these cellular immune-related lymphocyte subsets decreased in the noncompliant subjects. Although CD4 T-cell levels decreased in both groups, there was a significantly greater drop in the noncompliant patients. CD8+CD38+ T cells increased significantly in both groups. CONCLUSION Chronic DNCB application appears to have a beneficial clinical and immunomodulatory effect in HIV-infected patients.

Dendritic cells and dinitrochlorobenzene (DNCB): a new treatment approach to AIDS

Recent studies suggest that antigen-presenting cells (dendritic cells) may play a key role in the pathogenesis of human immunodeficiency virus (HIV) infection. This observation makes new immunomodulatory treatment strategies desirable. Topical dinitrochlorobenzene (DNCB) is discussed as a possible treatment modality in the context of its proven therapeutic uses and its immunomodulatory effect on dendritic cells. DNCB may be a safe, inexpensive, and widely available treatment option for HIV disease.

Morgellons disease: Analysis of a population with clinically confirmed microscopic subcutaneous fibers of unknown etiology

Background: Morgellons disease is a controversial illness in which patients complain of stinging, burning, and biting sensations under the skin. Unusual subcutaneous fibers are the unique objective finding. The etiology of Morgellons disease is unknown, and diagnostic criteria have yet to be established. Our goal was to identify prevalent symptoms in patients with clinically confirmed subcutaneous fibers in order to develop a case definition for Morgellons disease. Methods: Patients with subcutaneous fibers observed on physical examination (designated as the fiber group) were evaluated using a data extraction tool that measured clinical and demographic characteristics. The prevalence of symptoms common to the fiber group was then compared with the prevalence of these symptoms in patients with Lyme disease and no complaints of skin fibers. Results: The fiber group consisted of 122 patients. Significant findings in this group were an association with tick-borne diseases and hypothyroidism, high numbers from two states (Texas and California), high prevalence in middle-aged Caucasian women, and an increased prevalence of smoking and substance abuse. Although depression was noted in 29% of the fiber patients, pre-existing delusional disease was not reported. After adjusting for nonspecific symptoms, the most common symptoms reported in the fiber group were: crawling sensations under the skin; spontaneously appearing, slow-healing lesions; hyperpigmented scars when lesions heal; intense pruritus; seed-like objects, black specks, or “fuzz balls” in lesions or on intact skin; fine, thread-like fibers of varying colors in lesions and intact skin; lesions containing thick, tough, translucent fibers that are highly resistant to extraction; and a sensation of something trying to penetrate the skin from the inside out. Conclusions: This study of the largest clinical cohort reported to date provides the basis for an accurate and clinically useful case definition for Morgellons disease.

Musical hallucinations in patients with Lyme disease.

Musical hallucinations are poorly understood auditory hallucinations that occur in patients with otologic or neurologic diseases. We report the first cases of musical hallucinations in two patients with neurologic Lyme disease. Both subjects were women with clinical and laboratory evidence of chronic Lyme disease, progressive neurologic dysfunction, and abnormal magnetic resonance imaging of the brain. There was no evidence of hearing loss in either case. Musical hallucinations had a sudden onset and took the form of patriotic or operatic music. The auditory hallucinations disappeared with intravenous (IV) antibiotic therapy in both patients, but the hallucinations recurred when IV antibiotic therapy was discontinued in one case. Response to therapy was accompanied by an increase in the CD57 lymphocyte subset in one patient, whereas recurrent hallucinations were associated with persistently low CD57 levels in the other case. We conclude that musical hallucinations may be associated with neurologic Lyme disease. These auditory hallucinations appear to respond to IV antibiotic therapy. Patients with musical hallucinations of unknown cause should be tested for infection with the Lyme disease spirochete.

Filament formation associated with spirochetal infection: a comparative approach to Morgellons disease

Bovine digital dermatitis is an emerging infectious disease that causes lameness, decreased milk production, and weight loss in livestock. Proliferative stages of bovine digital dermatitis demonstrate keratin filament formation in skin above the hooves in affected animals. The multifactorial etiology of digital dermatitis is not well understood, but spirochetes and other coinfecting microorganisms have been implicated in the pathogenesis of this veterinary illness. Morgellons disease is an emerging human dermopathy characterized by the presence of filamentous fibers of undetermined composition, both in lesions and subdermally. While the etiology of Morgellons disease is unknown, there is serological and clinical evidence linking this phenomenon to Lyme borreliosis and coinfecting tick-borne agents. Although the microscopy of Morgellons filaments has been described in the medical literature, the structure and pathogenesis of these fibers is poorly understood. In contrast, most microscopy of digital dermatitis has focused on associated pathogens and histology rather than the morphology of late-stage filamentous fibers. Clinical, laboratory, and microscopic characteristics of these two diseases are compared.

Morgellons disease: the mystery unfolds

Morgellons disease is a mysterious skin disorder that was first described over 300 years ago. The disease is characterized by fiber-like strands extruding from the skin in association with dermatologic and neuropsychiatric signs and symptoms. Although Morgellons disease has been confused with delusional parasitosis, the occurrence of the disease in children, the lack of pre-existing psychopathology in most patients and the presence of subcutaneous fibers on skin biopsy indicate that the disease has a somatic origin. The association with Lyme disease and the apparent response to antibiotic therapy supports the concept that Morgellons disease may be triggered by an infectious process. Recent studies suggest that infection with Agrobacterium may play a role in the disease. Further clinical and molecular research is needed to unlock the mystery of Morgellons disease.

Searching for autoimmunity in “antibiotic-refractory” Lyme arthritis

In two recent articles published in Molecular Immunology, Steere and colleagues continue their search for an autoimmune mechanism of arthritis in patients who have failed short-course antibiotic therapy for Borrelia burgdorferi, the spirochetal agent of Lyme disease. As in previous attempts, the authors fail to elucidate a molecular mimicry mechanism for the putative autoimmune process, leading to the conclusion that there is no credible scientific evidence for a post-infectious autoimmune mechanism of arthritis in chronic Lyme disease.

Holmes-Adie syndrome and Lyme disease

anaesthesia we report might reflect the innervation of the breast, with infiltration being lateral to the breast lump and not into the lump itself, as well as the period of time allowed after infiltration before FNA was undertaken. Local anaesthesia has no adverse effect on diagnostic accuracy, and because the infiltration is lateral to the lump, palpation of the lump during aspiration is not obscured. We believe that the reduction of pain by local anaesthesia helps the tolerance of patients to the procedure and gives the operator a better chance of obtaining an adequate sample for diagnosis.

Lyme disease: scratching the surface

The excellent Comment by Ulrike Munderloh and Timothy Kurtti (Sept 17, p 962)1 describes the complex life cycle of Borrelia burgdorferi, the spirochaetal agent of Lyme disease, as it traffics between tick and mammalian hosts. The Comment highlights a growing problem with Lyme disease: while what is known about the basic science of this tick-borne illness becomes more complex, the clinical science remains relatively simplistic and uninformed.2 This divergence has produced a disconnection between the recognition of B burgdorferi as one of the most invasive and elusive bacteria known to man, and the clinical perception that Lyme disease is “hard to catch and easy to cure”.

Morgellons Disease: A Chemical and Light Microscopic Study

Morgellons disease is an emerging multisystem illness characterized by unexplained dermopathy and unusual skin- associated filament production. Despite evidence demonstrating that an infectious process is involved and that lesions are not self-inflicted, many medical practitioners continue to claim that this illness is delusional. We present relevant clinical observations combined with chemical and light microscopic studies of material collected from three patients with Morgellons disease. Our study demonstrates that Morgellons disease is not delusional and that skin lesions with unusual fibers are not self-inflicted or psychogenic. We provide chemical, light microscopic and immunohistological evidence that filaments associated with this condition originate from human epithelial cells, supporting the hypothesis that the fibers are composed of keratin and are products of keratinocytes.