A follow-up study of occupational styrene exposure and risk of autoimmune rheumatic diseases.

OBJECTIVES: Increased risk has been suggested for autoimmune rheumatic diseases following solvent exposure. The evidence for specific solvents is limited, and little is known about exposure-response relations. Styrene is an aromatic, organic solvent and the objective of this study was to analyse the association between occupational styrene exposure and autoimmune rheumatic diseases in men and women. METHODS: We followed 72 212 styrene-exposed workers of the Danish reinforced plastics industry from 1979 to 2012. We modelled full work history of styrene exposure from employment history, survey data and historical styrene exposure measurements. We identified cases in the national patient registry and investigated gender-specific exposure-response relations by cumulative styrene exposure for different exposure time windows adjusting for age, calendar year and educational level. RESULTS: During 1 515 126 person-years of follow-up, we identified 718 cases of an autoimmune rheumatic disease, of which 73% were rheumatoid arthritis. When adjusting for potential confounders and comparing the highest with the lowest styrene exposure tertile, we observed a statistically non-significantly increased risk of systemic sclerosis among women (incidence rate ratio (IRR)=2.50; 95% CI 0.50 to 12.50) and men (IRR=1.86; 95 % CI 0.50 to 7.00), based on 9 and 22 cases, respectively. Results were inconsistent for the other autoimmune rheumatic diseases examined. CONCLUSION: This study suggests an association between occupational styrene exposure and systemic sclerosis in men as well as in women but based on few cases. This is a new finding and has to be replicated before conclusions can be drawn.

Rheumatology in Poland.

The aim of this article is to present the current state of rheumatology in Poland, including the scientific and clinical activity and essential aspects of Polish rheumatic patients' treatment. PubMed, Scopus and Web of Science databases were searched for main keywords: "rheumat*" and affiliation with Poland. Statistical data were obtained from the Central Statistical Office, the National Health Fund and the Polish Chamber of Physicians and Dentists, while the public information from the Polish Society for Rheumatology, the Ministry of Health and the Ministry of Science and Higher Education. Databases of the World Health Organization, the Organization for Economic Co-operation and Development and the European Statistical Office (Eurostat) were used. Most Polish rheumatologists work in large urban agglomerations in the Mazovian, Malopolskie and Silesian Voivodeships. The rheumatologic infrastructure includes 1713 working rheumatologists (> 30% exceeding the age of 60 years), 2301 hospital beds, 2279 outpatient clinics and 955 private practices. Poland's state funding is relatively limited, this problem being addressed by health officials with special treatment programs for biological drugs. The Eurostat data indicate, that in Poland, like in the majority of EU Member States, there's a tendency of specialist/general practitioner ratio rising. The number of scientific publications by Polish rheumatologists has steadily increased in recent years. Poland's rheumatology has made an enormous progress at all levels of functioning in recent decades. The EULAR recommendations are mostly incorporated into the Polish health system, leaving still room for its further improvement in the fields of financing, therapy and education.

[Osteoporosis-frequent comorbidity in patients with rheumatism]. / Osteoporose ­ häufige Komorbidität bei Rheumapatienten.

Osteoporosis is one of the most frequent comorbidities in inflammatory rheumatic diseases. The immune system is substantially involved in the regulation of bone homeostasis and chronic inflammatory diseases influence this equilibrium at several levels. Besides the immunologically mediated inflammatory activity, immobility and glucocorticoid treatment are further risk factors for osteoporosis. Diagnostic and therapeutic recommendations are based on the current guidelines for osteoporosis of the Governing Body on Osteoporosis (DVO). Monitoring of the risk factors and bone mineral density testing is meaningful in each patient with a newly diagnosed rheumatic disease. In the case of a T-score ≤-1.5 a specific drug treatment with bisphosphonates, teriparatide or denosumab should be started together with optimizing preventive measures, such as reduction of glucocorticoid dosage, calcium and vitamin D intake and life style modifications. The risk of osteonecrosis of the jaw (ONJ) in patients with osteoporosis is small; however, there appears to be a significant increase in multiple vertebral fractures after discontinuation of denosumab.

Silicone breast implants and autoimmune rheumatic diseases: myth or reality.

PURPOSE OF REVIEW: In the present review, recent findings regarding silicone breast implants (SBIs) complicated by rheumatic autoimmune diseases are described. RECENT FINDINGS: Despite changes in the principal constituents of the silicone implants during the past 50 years, silicone remained an adjuvant that may 'bleed' and subsequently may be a chronic stimulus to the immune system resulting in similar clinical manifestations as 50 years ago. Silicones are spread throughout the body and can be detected in tissues and the central nervous system. Autoimmune/inflammatory syndrome by adjuvants (ASIA), allergies, autoimmune diseases, immune deficiencies and lymphomas occur in patients with SBIs. There is a need for adequately adjusted epidemiological studies to ascertain the frequency of these diseases. Explantation of the breast implants, however, should be advised to patients with complaints, as 60-80% of patients show an amelioration of the signs and symptoms after explantation. SUMMARY: SBIs are associated in a proportion of patients with complaints such as fatigue, cognitive impairment, arthralgias, myalgias, pyrexia, dry eyes and dry mouth. Silicones can migrate from the implant through the body and can induce a chronic inflammatory process. Explantation of SBI results in the majority of patients in an amelioration of the symptoms.

Impact of rheumatic diseases on oral health and quality of life.

OBJECTIVE: We investigated the effects of rheumatic diseases on oral symptoms, health habits, and quality of life in subjects with and without rheumatic diseases. The hypothesis was that patients with rheumatic diseases have more oral symptoms impairing their quality of life than healthy controls. METHODS: A questionnaire was mailed to a random sample of 1500 members of the Finnish Rheumatism Association, including those with and without rheumatic diseases. We focused on symptoms of the mouth and temporomandibular area, and health habits. Oral Health Impact Profile (OHIP14) was used to evaluate the oral health-related quality of life. We analyzed differences between subjects with and without rheumatic diseases, controlled for age, gender, smoking, and non-rheumatic chronic diseases. RESULTS: Completed questionnaires were received from 995 participants (response rate 66%). Of them, 564 reported rheumatic disease, 431 were used as controls. The patients reported significantly more all orofacial symptoms than controls. Severe dry mouth was reported by 19.6% of patients and 2.9% of controls (P < 0.001), and temporomandibular joint symptoms by 59.2% and 27.2% (P < 0.001), respectively. In the OHIP-14 questionnaire, the mean total score was significantly higher in patients (8.80 ± 11.15) than in controls (3.93 ± 6.60; P < 0.001). CONCLUSION: The study hypothesis was confirmed by showing that the patients with rheumatic diseases reported oral discomfort and reduced quality of life more often when compared with controls.

Influence of musculoskeletal conditions on oral health among older adults.

Both musculoskeletal disorders and diseases of the oral cavity are common and potentially serious problems among older persons, yet little attention has been given to the links between them. Several musculoskeletal diseases, including osteoporosis, Paget's disease, and arthritic disorders, may directly involve the oral cavity and contiguous structures. Drugs used to treat musculoskeletal diseases, including corticosteroids and bisphosphonates, increase the risk of suppression of the immune system and osteonecrosis of the jaw, respectively. Many people with disabling osteoarthritis, rheumatoid arthritis, and other conditions have difficulty practicing good oral hygiene and traveling to dental offices for professional help. Various inexpensive measures can help such individuals, including education of their caregivers and provision of antimicrobial mouthwashes and special toothbrushes.

Silicone breast implants and the risk of autoimmune/rheumatic disorders: a real-world analysis.

Objectives: Several epidemiological studies have investigated the link between silicone breast implants (SBIs) and autoimmune/rheumatic disorders, reporting inconsistent results. We aimed to evaluate the association between SBIs and the most clinically relevant autoimmune/rheumatic disorders using a large, population-based database. Methods: In this cross-sectional study, we used the computerized databases of Maccabi Healthcare Services (MHS), which include up to 20 years of data on 2 million members. Women with SBIs were identified by procedure and diagnosis codes, clinical breast examinations and mammography referrals. Autoimmune/rheumatic disorders were identified using the International Classification of Diseases 9th revision (ICD-9) codes. Multivariable logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). A Cox's proportional hazards model was used to calculate the hazard ratios (HRs) and 95% CIs among a subgroup of SBI recipients for whom the year of SBIs insertion was available. Results: We included 24 651 SBI recipients and 98 604 matched SBI-free women. The adjusted OR between SBIs and being diagnosed with any autoimmune/rheumatic disorders was 1.22 (95% CI 1.18-1.26). The strongest association with SBIs (OR > 1.5, p < 0.001) was recorded for Sjögren's syndrome, systemic sclerosis (SSc) and sarcoidosis (OR of 1.58, 1.63 and 1.98, respectively). Similar results were calculated when analysis was limited to women with no breast cancer history. A multivariable Cox regression model yielded a HR of 1.45 (95% CI 1.21-1.73) for being diagnosed with at least one autoimmune/rheumatic disorder in women with SBI compared with those without. Conclusions: SBIs seem to be associated with higher likelihood of autoimmune/rheumatic disorders diagnosis.

Prevalence of rheumatic musculoskeletal symptoms in rural and urban areas : a cross-sectional study in northern India.

OBJECTIVES: To study the prevalence of rheumatic musculoskeletal symptoms in rural and urban areas of Lucknow. METHOD: The survey was carried out in a cluster of rural (n = 5118) and urban (n = 5053) communities of Lucknow through a door-to-door survey. Demographic data were collected and subjects with musculoskeletal pain (MSK pain) were identified. A Hindi adapted version of the Community Oriented Program for the Control of Rheumatic Diseases questionnaire was used. Trained community volunteers completed the questionnaire. RESULTS: Present and past MSK pain was the most common self-reported problem in urban areas (34.1%), while it was the third most common self-reported problem in rural areas (15.1%), after abdominal pain and cough. Females (214.9 and 419.5 per 1000) were more affected than males (118.8 and 265.2 per 1000) in rural and urban areas, respectively. Point prevalence of MSK pain (pain in last week) was higher in urban areas (28.2%) compared to rural areas (14.1%). In rural as well as urban areas, knee (rural: 49.3%, urban: 50.6%) and spine (rural: 56%, urban: 43.6%) were highly reported pain sites. Fatigue ([n] rural: 328, urban: 368) weakness ([n] rural: 310, urban: 324) and anorexia ([n] rural: 84, urban: 142) were most common systemic symptoms reported by urban as well as rural people. Urethritis/balanitis and ulcers in the mouth were the most common other symptoms reported by people in both the areas. CONCLUSION: MSK pain is a predominant health problem of both rural and urban areas. Sex-adjusted prevalence is higher among females than males. Knee and back were highly prevalent pain sites in both rural and urban areas of Lucknow.

[Candida infections of the oral mucosa--not only a dental problem]. / Kandydoza blony sluzowej jamy ustnej problem nie tylko stomatologiczny.

UNLABELLED: Frequency of occurrence of mycotic infections of the oral mucosa is higher in later years. It is connected with common use of antibiotics, intensive cancer treatment (cytostatics, radiation therapy) as well as immunosuppressant drugs and antibiotics, which have an influence on mikroflora disorders of the oral cavity. Candidiasis of oral mucosa occurs in old patients, in people suffering from diabetes mellitus, hypothyreosis, sideropenia, hypovitaminosis and xerostomia, which is often caused by hypofunction of salivary glands during autoimmune diseases and/or drug and systemic treatment. The aim of the study was to make a retrospective evaluation of frequency of occurring mycotic infections in patients treated in the Department of Periodontology and Oral Mucosa Diseases, Medical University of Gdansk in the 2003, as well as recognition of systemic conditioning of these disorders. The Study material was clinical documentation of 4172 patients, treated because of different oral mucose and periodontium disorders. From these patients, selected was a group of 105 (83 women and 22 men) with diagnosis--Candidosis mucosae oris. Clinical and mycotic examination was performed. RESULTS: Mycotic infections were found in 105 patients (2.5%). Systemic diseases (74.3%) were found in a maturity of the patients, which indicated systemic predispositions to candida infections. CONCLUSION: A wide cooperation between general practitioners and dentists, especially perio-dontologists, is necessary to give full care to patients. Early diagnosis of disorders of the oral cavity of patients with systemic diseases and dentistry treatment or taking preventive measures seems to be necessary.

Connective tissue disease and other rheumatic conditions following cosmetic breast implantation in Denmark.

OBJECTIVE: To examine the occurrence of connective tissue diseases (CTDs) as well as ill-defined and other rheumatic conditions among Danish women with cosmetic silicone breast implants. PATIENTS AND METHODS: A total of 2761 women with breast implants and 8807 control subjects were identified from plastic surgery private clinics and from public hospital plastic surgery departments. Women operated on at plastic surgery private clinics were identified through the files of each clinic, while women operated on at public hospitals were identified using the nationwide Danish National Registry of Patients. The control group consisted of women who underwent cosmetic surgery other than breast implantation or who only had a consultation. All women were followed up from January 1, 1977, through December 31, 1996, through the Danish National Registry of Patients for the occurrence of CTD as well as ill-defined and other rheumatic conditions. For the study period January 1, 1977, through December 31, 1994, the Danish National Registry of Patients contains information on hospitalization only, whereas data on outpatient visits are included from 1995 on, thus improving the sensitivity of the data. The implant and control groups were compared with the Danish population rates for CTD and ill-defined and other rheumatic conditions, and a direct comparison between the implant and control groups was also performed. RESULTS: When compared with rates from the general population, no excess of definite CTD was observed in the implant cohorts. For ill-defined and other rheumatic conditions, statistically significant excesses of unspecified rheumatism were observed in both the implant and control cohorts when compared with national rates. A direct comparison between the implant and control cohorts found no material differences between the groups. CONCLUSIONS: The findings of this study support previous investigations and independent review panel conclusions that an association between silicone breast implants and definite CTDs is unlikely. The observation of an excess of unspecified rheumatism among women with implants and among control women suggests that women undergoing cosmetic plastic surgery have hospitalization rates for this condition in excess of those from the general population.

Epidemiology of silicone-related disease.

The epidemiology of silicone-related disease (SRD) is complicated by the variety of disease endpoints that have been associated with silicone exposure and the atypical nature of these diseases in silicone-exposed women. Current research reviewed here suggests that SRD may constitute a new disease entity, thus complicating disease definition and rendering studies of classic disease unlikely to detect risks of silicone exposure. This report addresses the most important study design issues (disease and exposure definitions, bias, confounding, and power) in the context of studies of SRD. The variety of silicones used complicates the definition of exposure for all studies, and for some populations simply determining who was implanted will be difficult. For any of these studies, inadequate patient follow-up is likely to underestimate disease risk. Studies of SRD are also complicated by confounding. That is, whether or not a woman chooses to receive an implant is related to her age, race, and other variables also related to rheumatoid and autoimmune disease. The absence of an appropriate control group also plaques published studies of silicone-related disease. Finally, inadequate sample size, resulting in studies of low statistical power, is a critical problem for rare diseases such as SRD. These points are illustrated using two published studies and five studies in progress.

The Tokelau Island migrant study: prevalence of various conditions before migration.

The Tokelau Island Migrant Study has shown no important differences between those who subsequently left their home islands to migrate to New Zealand and those who remained, in key anthropometric and biochemical variables already reported. This comparison is now extended to various common diseases and conditions, and again no major difference emerges. The Tokelauans are compared with other Polynesians and shown to have less diabetes, hypertension, effort pain, chronic bronchitis and varicose veins than New Zealand Maoris, while resembling some Cook Island groups. Changes in prevalences of some conditions following migration are postulated.

Long-term exposure to silicone breast implants does not induce antipolymer antibodies.

The focus of our studies was to determine whether the antipolymer antibody assay (APA) as an objective laboratory assay could contribute to the diagnosis in women with a silicone breast implant (SBI) and complaints/symptomatic disease. We investigated whether a population of symptomatic SBI recipients exists with a high prevalence of APA in the Netherlands. The study participants were selected based on self-reported complaints. In one study their physician was approached for additional information on their disease status. Two groups of 42 women were included in the studies, with a mean SBI exposure of 17 and 16 years, respectively. The participants were clinically examined, and the APA level in serum samples determined. The study population of SBI recipients was categorised in severity subgroups based on the functional capacity, and the study physicians general assessment of pain and disease activity. Positive APA levels were found in 10% of the SBI recipients. Also in control groups 8% showed a positive APA response. After categorisation most (65 of 84) SBI recipients belonged to the limited severity subgroup on an increasing scale of limited, mild, moderate and advanced. Eight were categorised in the mild, four in the moderate, and seven in the advanced severity subgroup. None of the APA positive women were found to belong to the moderate or advanced severity subgroup. Seven of the APA positive women belonged to the limited, and one woman to the mild severity subgroup. In conclusion, we were unable to include a large proportion of severely symptomatic SBI recipients in our study populations. So, we cannot confirm the results of Tenenbaum et al. [1] on the presence of APA in symptomatic SBI recipients. However, our failure in two separate studies to recruit symptomatic SBI recipients suggests that the population of severely symptomatic SBI recipients in the Netherlands is rather small. The number of APA positive responses in our study population was low. In addition, also in the normal population a similar low percentage of positively reacting women were observed. Hence, we cannot recommend the use of the APA assay for diagnostic purposes in the clinical evaluation of SBI recipients with severe complaints/symptoms.

First evaluation study of the Dutch Working Party on silicone breast implants (SBI) and the silicone-related symptom complex (SRSC).

This cohort study evaluates the postoperative prevalence of antinuclear antibodies (ANA) in relation to symptoms related to the so-called silicone-related symptom complex (SRSC). A total of 63 women who underwent mastectomy followed by immediate breast reconstruction with a silicone implant (SBI) between Septembber 1990 and May 1995 at the University Hospital Rotterdam/Daniel den Hoed Cancer Center, participated voluntarily in the study. Their sera were tested for the presence of antinuclear antibodies (ANA) and at the same time they were screened for the prevalence of SRSC-related symptoms by questionnaire. All patients were also examined physically. Sixteen per cent of the women were ANA positive. There was no difference in SRSC expression between ANA-positive and ANA-negative women. The lack of difference in symptom expression between the ANA-positive and ANA-negative women and the rather low complaint percentage proves that if ANA positivity is related to the SRSC, we found no evidence that patients with a SBI with a positive ANA differed from the ANA-negative patients.

Rheumatic manifestations in danish women with silicone breast implants.

The aim of this study was to investigate whether women with silicone breast implants (SBI) present with a unique rheumatic symptomatology. We assessed the profile of rheumatic disease in six groups of women identified through Danish hospital and population registers, three groups of women with a prior hospital diagnosis of muscular rheumatism (a non-specific diagnostic code) who had previously undergone SBI surgery (n = 28), breast reduction surgery (n = 29) or no breast surgery (n = 27); and three groups of women without a diagnosis of muscular rheumatism who had undergone SBI surgery (n = 21), breast reduction surgery (n = 27) or no breast sugery (n = 56). All women in the study population (n = 188) underwent a thorough clinical examination, blood tests and a personal interview. In all study groups soft-tissue rheumatism and degenerative diseases were the most frequent diagnoses. Women with a prior diagnosis of muscular rheumatism but no prior breast surgery had a significantly higher prevalence of soft-tissue rheumatism than those with breast implant or reduction surgery. No significant differences in the frequencies of rheumatic diseases were observed among the three groups of women without previous muscular rheumatism. No specific pattern of inflammatory rheumatic disorders or soft-tissue complaints was identified among the women with SBI, and blood tests for autoimmunity revealed no unique pattern. Overall, women with earlier rheumatism had significantly increased frequencies of rheumatic conditions than did those without. We found no evidence of a rheumatic symptomatology unique to women with silicone breast implants. Our study emphasises the need for consideration of prior rheumatic disease when evaluating rheumatic manifestations in women with SBI.

Self-reported diseases and symptoms by rupture status among unselected Danish women with cosmetic silicone breast implants.

Epidemiologic evidence does not support an association between silicone breast implants and connective tissue or other rheumatic diseases. However, a recent study has suggested that women with ruptured implants may be at increased risk of developing fibromyalgia. An analysis of adverse health outcomes according to breast implant rupture status was conducted in 238 unselected Danish women with cosmetic silicone breast implants. Ninety-two of the women had definite implant rupture, and 146 had intact implants as determined by magnetic resonance imaging. Before undergoing imaging, the women provided blood samples and completed a self-administered questionnaire. Women with ruptured implants overall, and the subgroup with extracapsular ruptures (n = 23), were compared with women with intact implants regarding a number of self-reported diseases and symptoms and the presence of specific autoantibodies, such as antinuclear antibodies, rheumatoid factor, and cardiolipin immunoglobulin G and M antibodies. Overall, there were no differences in the occurrence of self-reported diseases or symptoms or in the presence of autoantibodies between women with intact implants and women with ruptured implants, including extracapsular rupture. The only exception was capsular contracture, which was reported six times more frequently by women with extracapsular ruptures than by women with intact implants (OR, 6.3; 95 percent CI, 1.7 to 23.5). In conclusion, this study of unselected women with silicone breast implants could establish no association between silicone implant rupture and specific diseases or symptoms related to connective tissue disease or other rheumatic conditions, except for an excess of capsular contracture among women with extracapsular rupture.

Antipolymer antibodies in Danish women with silicone breast implants.

OBJECTIVE: To use a new immunologic assay to evaluate antipolymer antibody (APA) levels among women with silicone breast implants (SBIs). METHODS: Women (n = 186) were identified through Danish population-based registers and categorized into six groups defined by prior breast surgery (silicone breast implantation/breast reduction/no breast surgery) and by the presence or absence of a prior hospital diagnosis of soft-tissue rheumatism (muscular rheumatism, ICD-8 codes 717.90 and 717.99). The women underwent blood tests, including an APA test, a clinical examination, and an interview focusing on rheumatic complaints. Blood samples were tested blindly. The severity of rheumatic symptoms/signs was scored from 1 (none) to 5 (severe) based on the clinical examination and interview. RESULTS: Women with SBIs did not have higher levels of APA than women without SBIs. The majority of women with SBIs had mild rheumatic complaints, and the severity of their symptoms was not related to APA levels. Among women who had previously been hospitalized because of soft-tissue rheumatism, there were more fibromyalgia cases, and their symptoms were more severe compared with those women without prior soft-tissue rheumatism; however, APA levels were not higher among these women. There was a significant difference in APA measurements resulting from between-kit variation (p less 0.01). CONCLUSIONS: Our data did not demonstrate higher APA levels among women with SBIs compared with controls. The large variation observed between the individual plates in the APA test should be evaluated in future studies.

Mouth and genital ulcerations in the community.

OBJECTIVE: To estimate the prevalence of mouth and genital ulceration in the community and its relationship to rheumatic diseases. METHODS: A house to house survey was carried out over a period of 18 months extending from September 1993 to February 1995, on 5,894 individuals utilizing detailed questionnaires on symptoms of musculoskeletal diseases and associated symptoms including history of mouth, genital ulcers, eye symptoms, and skin changes. After the initial phase, a 2nd phase was completed by trained nurses and paramedical staff, the purpose of which was to explore in detail, the history of those responding positively to any of the questions in phase one. The 3rd stage was conducted by general practitioners and rheumatologist to interview and examine those identified in phase 2 at King Fahad Hospital, Buraidah, Kingdom of Saudi Arabia. RESULTS: We identified 7 (0.1%) cases of genital ulceration, 43 (0.7%) cases of mouth ulceration, 263 (4.5%) cases of reddish eye or blurred vision, and 124 (2.1%) cases of skin rashes. Only 2 cases had both mouth and genital ulceration in addition to eye disease, skin rash and musculoskeletal pain. There was significant correlation between mouth ulcers and skin rash, eye symptoms, genital ulcerations, male sex, single status, weight loss and backpain. CONCLUSION: The vast majority of mouth and genital ulcers are not associated with a known rheumatic disease.

[Rheumatic manifestations of acquired immunodeficiency syndrome (AIDS)]. / Manifestações reumáticas na síndrome de imunodeficiência adquirida (AIDS).

120 AIDS patients (mean age 33 +/- 9 years, 108 males) were evaluated regarding rheumatic manifestations. According to CDC's classification, 18.3% belonged to group II, 28.3% to group III, and 53.4% to group IV. Arthralgia was present in 33 patients (27.5%), and in only 8 could be associated with infections other than HIV (5 cases of tuberculosis, 3 P. carinii, and 1 gonococcal infection). Incidence of arthralgia was equal in either sex. Arthritis was present in 8 patients, 2 of them with Reiter's syndrome. In 6 patients arthralgia was the first symptom (3 with arthritis) before AIDS diagnosis. There was a higher incidence of dry mouth, dry eyes, and muscular complaints in patients with arthralgia than in patients without arthralgia. Antinuclear antibodies and rheumatoid factor were absent in the serum of the patients studied. Arthritic manifestations possibly occur in AIDS, even in patients without other clinical manifestations, as a reactive state to HIV infection.