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1/14. The spectrum of chronic inflammatory demyelinating polyneuropathy.

    research criteria for the diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) were proposed by an Ad Hoc Subcommittee of the American Academy of neurology (AAN) in 1991, and since then these criteria have been widely used in clinical studies. We have been impressed by the frequent finding of electrophysiological changes of a demyelinating neuropathy in patients whose clinical presentation does not conform to the usually accepted clinical phenotype of CIDP. To determine the clinical spectrum of CIDP, we conducted a retrospective review of patients of the peripheral electrophysiology laboratory of the University of Miami-Jackson Memorial Medical Center. Diagnostic criteria for acquired demyelination of an individual nerve were adapted from the AAN research criteria for the diagnosis of CIDP (1991). patients were accepted for inclusion when such evidence was demonstrated in at least one motor nerve or at least two sensory nerves. We then reviewed the clinical phenotype and the underlying etiology of the neuropathy in these cases. Eighty-seven patients, 63 male and 24 female, age of onset 4-84 (mean 49.3) years, met these inclusion criteria. Forty-seven patients (54%) had distinct features outside the usual clinical presentation of CIDP. Of these, 15 (17%) had predominantly distal features, 13 (15%) had exclusively sensory polyneuropathy; seven (8%) had markedly asymmetric disease, seven (8%) had associated CNS demyelination, four (5%) had predominant cranial nerve involvement, and one (1%) had only the restless legs syndrome. An associated medical condition that may have been responsible for the acquired demyelinating neuropathy was present in 60% of the patients. We conclude that spectrum of CIDP is broader than would be indicated by the strict application of the AAN research criteria, and that many of the cases meeting more liberal criteria frequently respond to immunosuppressive therapy.
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2/14. Infection-triggered anorexia nervosa in children: clinical description of four cases.

    BACKGROUND: anorexia nervosa (AN) is a serious illness with no definitive treatment. Clinical and research evidence led to the hypothesis that some children with AN may have a pediatric autoimmune neuropsychiatric disorder associated with streptococcus (PANDAS), similar in pathogenesis to other hypothesized PANDAS disorders. methods: Four youngsters (ages, 11-15 years) with PANDAS AN were treated with an open trial of antibiotics, in addition to conventional treatment. They were evaluated for eating disorder and obsessive-compulsive symptoms, and for weight gain. Evidence of streptococcal infection came from clinical evaluation, throat cultures, and two serological tests: anti-deoxyribonuclease B (anti-DNase B) and anti-streptolysin O (ASO) titers. The "rheumatic" marker D8/17 was also measured. This B-cell alloantigen is associated, in several publications, with poststreptococcal autoimmunity: rheumatic fever (RF), Sydenham's chorea (SC), and possibly PANDAS obsessive compulsive disorder (OCD) and tic disorders. RESULTS: There was clinical evidence of possible antecedent streptococcal infection in all four patients, two of whom had comorbid OCD, with possible infection-triggered AN. All four had the rheumatic marker: A percentage of D8/17-positive B cells of 28-38%, with a mean of 33% (12% or more is considered positive for the marker). The patients responded to conventional treatment plus antibiotics with weight restoration and decreased eating disorder and obsessive-compulsive symptoms. Three needed to gain weight and did so. CONCLUSIONS: There may be a link between infectious disease and some cases of AN, which raises the possibility of new treatment.
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3/14. Pediatric autoimmune neuropsychiatric disorders and streptococcal infections: role of otolaryngologist.

    OBJECTIVE: To increase awareness and understanding of the putative role of streptococcal infection in the development of neuropsychiatric disorders in children and to discuss therapeutic options in this group of patients. methods: Case illustration and literature review. RESULTS: Two siblings, one with obsessive-compulsive disorder (OCD) and one with a tic disorder, had tonsillectomy for recurrent streptococcal pharyngitis. At the latest follow-up visit (11 mo postoperatively), both patients exhibited significant improvement in their psychiatric illnesses. We discuss these cases as well as the diagnosis, pathophysiology, and treatment of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). CONCLUSION: PANDAS is an active area of research investigating the relationship between streptococcal infections and the development of obsessive-compulsive disorder or tic disorders (or both) in children. The etiopathogenesis of PANDAS is thought to reflect autoimmune mechanisms and involvement of the basal ganglia of susceptible hosts. Because otolaryngologists evaluate a large portion of pediatric patients with recurrent streptococcal pharyngitis, it is important to be aware of this association and to manage these patients appropriately.
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4/14. Autoimmune progesterone dermatitis and its manifestation as anaphylaxis: a case report and literature review.

    OBJECTIVE: Autoimmune progesterone dermatitis is a rare cyclic premenstrual reaction to progesterone produced during the luteal phase of a woman's menstrual cycle with a variety of presentations including erythema multiforme, eczema, urticaria, angioedema, and progesterone-induced anaphylaxis. We present a case of progesterone-induced anaphylaxis and a review of literature focusing on its diagnosis and therapy. DATA SOURCES: We surveyed all the literature in English back to 1921 when the first case was published. First, we researched the terms progesterone anaphylaxis, autoimmune progesterone dermatitis, cyclic urticaria, using the pubmed resource. Then we included articles found within these publications' reference sections. STUDY SELECTION: We selected articles based on whether the cases described appeared to fit the description of the entity autoimmune progesterone dermatitis. All cases included had dermatologic reactions occurring during the luteal phase of the menstrual period, positive skin or intramuscular reactions to progesterone, and treatment amenable to anovulatory agents and/or hysterectomy with bilateral salpingo-oophorectomy. RESULTS: We found approximately 50 published cases of autoimmune progesterone dermatitis, and only nine known cases of its manifestation as anaphylaxis. These cases, including the case described by us, are summarized, and successful diagnostic and therapeutic approaches in the literature are reviewed. CONCLUSIONS: Autoimmune progesterone dermatitis is a rare entity associated with progesterone production of the luteal phase of a woman's menstrual cycle. It can be diagnosed using intradermal or intramuscular progesterone tests and can be treated by disrupting the ovulation cycle using specific medications or by oopherectomy.
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5/14. Childhood-onset obsessive-compulsive disorder and tic disorders: case report and literature review.

    A subgroup of childhood-onset obsessive-compulsive disorder (OCD) and tic disorders has been found to have a postinfectious autoimmune-mediated etiology. Clinical observations and systematic investigations have shown that a subgroup of children with OCD and/or tic disorders have the onset and subsequent exacerbations of their symptoms following infections with group A beta-hemolytic streptococci (GABHS). This subgroup has been designated by the acronym PANDAS: pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. Five clinical characteristics define the PANDAS subgroup: presence of OCD and/or tic disorder, prepubertal symptom onset, sudden onset or abrupt exacerbations, association with neurological abnormalities during exacerbations (adventitious movements or motoric hyperactivity), and the temporal association between symptom exacerbations and GABHS infections. The proposed poststreptococcal inflammatory etiology provides a unique opportunity for treatment and prevention, including immunomodulatory therapies such as plasma exchange and intravenous immunoglobulin. A placebo-controlled trial revealed that both intravenous immunoglobulin and plasma exchange were effective in reducing neuropsychiatric symptom severity (40 and 55% reductions, respectively) for a group of severely ill children in the PANDAS subgroup. Further research is required to determine why the treatments are helpful and to ascertain whether or not antibiotic prophylaxis can help prevent poststreptococcal symptom exacerbations.
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6/14. Activation of autoimmunity following use of immunostimulatory herbal supplements.

    BACKGROUND: Evidence for the scientific basis of purported therapeutic effects and adverse effects of herbal supplements continues to grow. Many herbal supplements are touted for their immunostimulatory properties, and both in vitro and in vivo experiments have supported this claim. Although this explains their beneficial effects in preventing or curtailing disease, to our knowledge, no immunostimulatory herbal supplements have been reported to exacerbate disorders of immune system overactivity. OBSERVATIONS: We describe 3 patients whose autoimmune disease onset and/or flares correlated with ingestion of herbal supplements with proven immunostimulatory effects. echinacea and the alga spirulina platensis are implicated in 2 patients' flares of pemphigus vulgaris, and a supplement containing the algae spirulina platensis and aphanizomenon flos-aquae was ingested by a third patient days before both onset and a severe flare of dermatomyositis. The third patient showed heterozygosity for a tumor necrosis factor alpha (TNF-alpha) promoter polymorphism (-308A), leading to increased production of TNF-alpha, which may have predisposed her to developing dermatomyositis. CONCLUSIONS: Immunostimulatory herbal supplements may exacerbate preexisting autoimmune disease or precipitate autoimmune disease in persons genetically predisposed to such disorders. Increased production of TNF-alpha may play a role, although more research is needed to clarify the mechanisms of such phenomena.
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7/14. cytomegalovirus-associated periodontitis and guillain-barre syndrome.

    BACKGROUND: guillain-barre syndrome (GBS), an autoimmune disorder of the peripheral nervous system, is characterized by rapidly ascending neural paralysis, hyporeflexia, and areflexia. The polyneuropathy of the GBS affects one to four humans per 100,000 of the population annually throughout the world (adults and children). The pathogenesis of GBS remains unclear. However, there are increasing indications that the disease is triggered by a preceding well-established febrile infection by cytomegalovirus (CMV). The present report describes active CMV within the periodontium of a 37-year-old patient affected by GBS. methods: Real-time reverse transcriptase-polymerase chain reaction (real-time RT-PCR) was performed to detect CMV, Epstein-Barr virus-1 (EBV-1), herpes simplex 1 (HSV-1) and 2 (HSV-2) virus, and enteroviruses (polio-, coxsackie-, echo-, and enteroviruses 68 and 71) from periodontal sites demonstrating advanced attachment loss. Healthy sites and sites with inflamed gingival tissue were not included in the study. Anaerobic bacterial culture determined the occurrence of potential major periodontal pathogens. RESULTS: Real-time RT-PCR and microbiologic analysis revealed the presence of a dual infection of CMV and specific bacterial plaque. CMV, porphyromonas gingivalis, Tannerella forsythensis, and campylobacter species were associated with periodontitis active sites, loss of attachment, and gingival bleeding. Furthermore, periodontal sites infected by active CMV had no visible radiographic crestal lamina dura. CONCLUSIONS: The periodontium may serve as a reservoir for CMV and a source of viral replication. However, further research is needed to test whether viral replication in the periodontium precedes the GBS symptoms.
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8/14. An informative case of Graves' disease with implications for schizophrenia.

    The aetiology of schizophrenia and the other psychoses is not yet established. The Knight model, based on genetic and other evidence, proposes that schizophrenia is an autoimmune disease, caused by the development of forbidden clones of B lymphocytes that secrete autoantibodies that accidentally stimulate cell surface receptors on certain neurons, affecting the limbic system of the brain. An unusual defect in a Maori man with Graves' disease rendered him unresponsive to the usually effective antithyroid drugs, prompting his being treated with prednisone, a non-specific immunosuppressant agent. This was highly successful, reducing the blood level of the causative thyroid-stimulating autoantibodies with reduction of thyroid hormone levels and thyroid gland size. Unfortunately, high dosage prednisone can be used for only a month, because of steroid toxicity. A research pathway to effective therapy of receptor-mediated autoimmune diseases, which probably include the psychoses, is now apparent. It involves finding the autoantibodies, then cloning of their antigenic targets, as has been done for Graves' disease. This will provide knowledge of the peptide sequences necessary for constructing therapeutic agents for selectively destroying the pathogenic forbidden clones. Meanwhile, usage of short-term therapy with prednisone could be helpful in the management of schizophrenia and should be explored.
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9/14. purpura fulminans as clinical manifestation of atypical SLE with antiphospholipid antibodies: a case report.

    purpura fulminans and DIC were the main clinical manifestations of the antiphospholipid syndrome observed in a 62-year-old man. The patient was well until 44 years of age when he began to suffer from recurrent thrombophlebitis, without other symptoms suggestive of immune disease. At the time of hospital admission the pt. appeared acutely ill, showing high fever, severe anemia, massive urinary blood loss, multiple purpuric patches evolving to hemorrhagic bullae and gangrene rapidly spreading over about 30% of the total body area. No signs of neurological involvement or of visceral thrombotic occlusions were present. Clotting tests were consistent with a diagnosis of DIC, further confirmed by skin biopsy showing the presence of thrombi in dermal arterioles. The autoantibody research was positive as follows: Waaler-Rose 1:40, Anti-dna 1:80; ANF 1:640, aCA IgG 100 GPL. LA was diagnosed according to standard criteria: prolonged KCT and RVVT not corrected by a mixture of normal plasma and abnormal TTI. plasma exchange in association with heparin and prednisone was effective in arresting the progression of the skin lesion; nevertheless the patient died ten days after hospital admission for sepsi and acute renal failure.
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10/14. pemphigus in families.

    A family in which two sisters are affected by pemphigus is described. literature research has revealed the presence of 25 families, comprising 53 patients, in which pemphigus existed in more than one member. The relationships between those affected were mainly parent-child or sibling-sibling. pemphigus was found to be associated with specific hla antigens: A26, Bw38, DRw4, and additionally occurred with a higher frequency in certain ethnic groups. The variety of etiologic factors in the pathogenesis of pemphigus is discussed and the significance of a genetic role elucidated.
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