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OBJECTIVE: To describe patients with rheumatoid arthritis (RA) who subsequently developed bronchiectasis (BR) and to review the literature on biologic response modifiers (BRM) in relation to infectious complications in the management of these patients. METHODS: We describe 4 patients with RA who were diagnosed with BR out of a cohort of 170 patients. We then performed a comprehensive review of the English language literature on the major clinical trials for RA that involved the BRMs etanercept, infliximab, anakinra, and adalimumab. We focused on inclusion/exclusion criteria involving pulmonary disease and infectious complications in these trials. RESULTS: Of the 4 patients we describe, all developed BR after the diagnosis of RA was established, had positive cyclic citrullinated peptide antibodies, had extra-articular manifestations, and had clinical courses complicated by pneumonia. Management strategies were influenced by these factors in all of the patients described. Of the 16 clinical trials on BRMs reviewed, few studies mentioned BR as an exclusion criteria or reported pneumonia as a specific infectious complication. CONCLUSIONS: BR may be considered as an extra-articular pulmonary manifestation of RA. The infectious complications associated with BR in these patients underscore the management challenge, especially in choosing whether or not to treat with BRMs. Further studies are needed to analyze the infectious complications in RA trials with BRMs, specifically, to assess the risk of patients with BR. Risk stratification in these patients may require screening them for the presence of underlying BR. Copyright © 2006 by Elsevier Inc. [ABSTRACT FROM AUTHOR]

Background: Many patients with polymyositis (PM) or dermatomyositis (DM) have circulating myositis-specific antibodies (MSAs). Interstitial lung disease (ILD) is a common manifestation of PM/DM, and it can even precede the onset of characteristic muscle or skin manifestations. Furthermore, there appear to be some patients with ILD and circulating MSAs who do not develop muscle or skin disease even after prolonged follow-up. We sought to determine whether ILD is equally or more common than myositis or dermatitis at the time of initial detection of MSAs., Methods: We identified all patients found to have circulating MSAs at our institution over a 4-year period and assessed for the presence of lung, muscle, and skin disease at the time of initial detection of MSAs. Among those found to have ILD, we compared demographic and clinical features, chest CT scan findings, and outcomes between those with PM/DM-associated ILD and those with ILD but no muscle or skin disease., Results: A total of 3078 patients were tested for MSAs, and of these 40 were positive. Nine different MSAs were detected, with anti-histidyl tRNA synthetase (anti-Jo-1) being the most common (35% of MSAs). Among patients with positive MSAs, 86% were found to have ILD, compared to 39% and 28% with muscle and skin involvement, respectively (p < 0.001). Fifty percent of all MSA-positive patients had isolated ILD, with no evidence of muscle or skin disease. Those with isolated ILD were more likely to be older and have fibrotic changes on chest CT, less likely to receive immunomodulatory therapy, and had worse overall survival., Conclusions: In this study we found that individuals with circulating MSAs were more likely to have ILD than classic muscle or skin manifestations of PM/DM at the time of initial detection of MSAs. Our findings suggest that the presence of ILD should be considered a disease-defining manifestation in the presence of MSAs and incorporated into classification criteria for PM/DM., (© 2021. The Author(s).)

Musculoskeletal symptoms in Lyme disease are very common at all stages of the disease. Lyme arthritis, whether intermittent or chronic, is a hallmark of late Lyme disease. This may cause severe joint pain and swelling especially confined to one or a few joints, most notably the knee. Antibiotic therapy is very effective in treating Lyme arthritis in the majority of cases. However, a small proportion of individuals will develop persistent chronic arthritis which is likely mediated through immunologic mechanisms. In these patients treatment strategies should include anti-inflammatory medications and possibly immunosuppressive treatments. Arthroscopic synovectomy ma ybe very helpful in some of these patients. Post Lyme disease syndrome and Lyme myositis are two other sequelae that are associated with Lyme disease.

Multicentric reticulohistiocytosis is a rare granulomatous disease of unknown etiology, characterized by cutaneous nodules and destructive arthritis. Skin lesions can cause significant deformity, and approximately half of affected patients develop a severe disabling arthritis. The disease is often associated with malignancy; however, the paraneoplastic nature of multicentric reticulohistiocytosis is not established. The diagnosis is confirmed by the presence of oncocytic ("ground-glass") histiocytes and multinucleated giant cells on histopathology of the cutaneous nodules and the synovial membrane.

Objective: To estimate minimally important differences (MIDs) in scores for the modified Rodnan Skin Score (mRSS) and Health Assessment Questionnaire-Disability Index (HAQ-DI) in a clinical trial on diffuse systemic sclerosis (SSc)., Participants and Methods: 134 people participated in a 2-year, double-blind, randomised clinical trial comparing efficacy of low-dose and high-dose D-penicillamine in diffuse SSc. At 6, 12, 18 and 24 months, the investigator was asked to rate the change in the patient's health since entering the study: markedly worsened, moderately worsened, slightly worsened, unchanged, slightly improved, moderately improved or markedly improved. Patients who were rated as slightly improved were defined as the minimally changed subgroup and compared with patients rated as moderately or markedly improved., Results: The MID estimates for the mRSS improvement ranged from 3.2 to 5.3 (0.40-0.66 effect size) and for the HAQ-DI from 0.10 to 0.14 (0.15-0.21 effect size). Patients who were rated to improve more than slightly were found to improve by 6.9-14.2 (0.86-1.77 effect size) on the mRSS and 0.21-0.55 (0.32-0.83 effect size) on the HAQ-DI score., Conclusion: MID estimates are provided for improvement in the mRSS and HAQ-DI scores, which can help in interpreting clinical trials on patients with SSc and be used for sample size calculation for future clinical trials on diffuse SSc.

We describe the case of a patient with polymyositis and anti-Jo-1 antibodies who experienced a relapse of his inflammatory muscle disease after 7 years of clinical remission. Our review of the literature shows that remission is achieved in 25-68% of patients treated with high dose corticosteroids as part of their initial therapy. Relapse rates after complete remission vary from 6 to 43% in the few studies where this information is available. Late relapses after initial remission appear to be unusual, but may be more frequent in patients like this one with antisynthetase syndrome.

Two cases of septic sacroiliac (SI) joint arthritis are presented to illustrate the difficulty of diagnosing and treating this uncommon osteoarticular infection. The patients presented are a 68-year-old woman with septic sacroiliitis caused by Streptococcus agalactiae and a 20-year-old man with Salmonella infantis infection involving the SI joint. The recent literature is reviewed and compared with previously published series. Of the 177 cases we reviewed, 47 (27%) occurred in pediatric patients. The mean age was 20 years. Only six patients (3%) were older than 60 years of age. Magnetic resonance imaging (MRI) is most useful for defining extent of infection, osteomyelitis, and abscess formation in the SI joint. Computed tomography (CT) is valuable for defining the extent of bone involvement and for guidance of percutaneous needle arthrocentesis. Other imaging modalities are useful primarily in the initial evaluation of patients with a nonspecific presentation. Four to six weeks of intravenous (i.v.) antibiotic therapy is recommended. Indications for surgical intervention include abscess formation, osteomyelitis, sequestrum of necrotic bone, and failure to respond to i.v. antibiotic therapy.

A case of limited cutaneous systemic sclerosis with severe diffuse subcutaneous calcification is presented. The patient experienced multiple complications of calcinosis from this condition and was completely resistant to all treatment modalities. A detailed analysis of the calcific crystals revealed hydroxyapatite and octacalcium phosphate. Possible treatment strategies for calcinosis in scleroderma are reviewed in the context of this case.

Objective: To measure the urinary excretion of specific cross-link amino acid markers for mature elastin (desmosine [DES] and isodesmosine [IDES]) and fibrillar collagen (hydroxylysylpyridinoline [HP] and lysylpyridinoline [LP]) in systemic sclerosis (SSc) patients and healthy controls., Methods: Urine specimens from 20 patients with SSc and 22 controls were assessed for DES, IDES, HP, and LP using high performance liquid chromatography and ultraviolet absorption spectroscopy, in combination with an isotope dilution technique in which the urine specimen was spiked with isotopically labeled cross-link amino acids., Results: Mean +/- SD levels of urinary DES and IDES were elevated in SSc patients by 2-3-fold, and urinary HP and LP by 3-4-fold, compared with controls (DES 21.0 +/- 9.4 versus 7.5 +/- 1.4 micrograms/gm creatinine; HP 109.0 +/- 72.9 versus 24.9 +/- 5.7 nmoles/mmole creatinine). Nineteen of the 20 SSc patients had urinary DES and HP values that were > 3 SD above the control mean. A significant elevation in the HP:LP ratio in SSc patients as compared with controls (mean +/- SD 6.9 +/- 1.5 versus 5.5 +/- 1.3) indicated a soft tissue origin for much of the increased HP., Conclusion: Patients with SSc have higher levels of urinary cross-link amino acids specific for the degradation of mature collagen and elastin. These markers distinguish most SSc patients from healthy controls.

Raynaud's phenomenon occurs in about 5% of the adult population, and most individuals do not seek medical attention for the condition. In symptomatic patients with Raynaud's phenomenon, it is useful to categorize the condition as primary or secondary. In addition to providing a framework for epidemiologic and therapeutic protocols, such classification may reflect basic pathophysiologic differences. Occupation-related Raynaud's phenomenon has been recognized recently as a major cause of lost wages and productivity. Neurogenic and "local fault" hypotheses to explain primary Raynaud's phenomenon are still being studied. In secondary Raynaud's phenomenon, obliterative arteriopathy and the role of endothelial-derived products have been the focus of intense research interest. Under some circumstances, the combination of nailfold capillary microscopy and autoantibody analysis can identify patients with primary Raynaud's phenomenon that is likely to evolve into a secondary form of Raynaud's phenomenon. Although information from this type of analysis may be overinterpreted, the prognostic yield is highest for patients destined to develop systemic sclerosis-related disorders. Newer vasodilating agents and antithrombotic drugs may offer benefit for patients with both primary and secondary Raynaud's phenomenon.

The affect of host and donor related factors on successful engraftment of human cells into mice was examined to minimize the variability that has been observed in successful development of human-mouse chimera for the study of human disease and immune physiology and regulation. Human immunoglobulin production in severe combined immunodeficiency (SCID) mice engrafted with human peripheral blood mononuclear cells (PBMC) was augmented by immunosuppressing recipient mice and activating donor PBMC. Immunosuppression of recipient mice with 3 Gy of gamma-irradiation induced a 10-fold increase in human IgG in the sera of engrafted SCID mice. Variation in production of human IgG in recipient mice correlated with preinjection phenotype and activation status of injected PBMC. Mice injected with PBMC with a low CD4/CD8 ratio (less than 0.5) produced no detectable circulating human immunoglobulin. When the CD4/CD8 ratio was greater than 1.5, human IgG was detected in sera of PBMC-recipient SCID mice. Serum IgG increased 10-fold following in vitro activation of donor PBMC with anti-CD3, IL-2 and Staphylococcus aureus. Successful engraftment and serum IgG production was evidenced by an increase in the recovery of activated human IgG+ cells in the spleens of mice with maximal IgG production. Optimization of functional engraftment required modification of both the host (SCID mice) and the donor cells.

Two cases of cryptococcal meningitis occurring in patients with systemic lupus erythematosus (SLE) are presented, and 24 additional cases from the literature are reviewed. The insidious onset of this infrequent complication is emphasized. The nonspecific neurological findings associated with this infection are often mistakenly diagnosed as a central nervous system manifestation of SLE. Earlier diagnosis and effective antifungal therapy have improved the prognosis of cryptococcal meningitis in SLE patients in recent years. Strategies for the treatment of patients with this complication are discussed.

We describe a patient with Sezary syndrome and seronegative symmetric polyarthritis. Detailed analysis of the synovial membrane, including T lymphocyte subset delineation, demonstrated that malignant synovial infiltration was the direct cause of arthritis in this patient.

A patient with systemic lupus erythematosus and numerous thrombotic accidents was found to have a deficiency of the free fraction of protein S, most likely due to an abnormally high level of C4b binding protein. These abnormalities, unique in comparison to 4 other patients with hypercoagulation states, were partially corrected with cyclophosphamide. There was no evidence of a consumption of complement components. The interactions between the hemostasis system and the complement cascade are discussed.

Human monoclonal antibodies reactive with type II collagen were obtained from patients with rheumatoid arthritis and relapsing polychondritis by fusion of cells with the human-mouse myeloma analogue HMMA2.11 TG/0. Direct fusion of peripheral blood or bone marrow mononuclear cells was unsuccessful in obtaining antibody producing hybridomas although fusion efficiency was high (1 hybridoma per 25,400 mononuclear cells fused). Polyclonal, Epstein Barr Virus transformed B cell lines derived from peripheral blood and bone marrow mononuclear cells after direct transformation, in vitro secondary immunization, and/or CD8 depletion were found to produce antibodies that reacted with type II collagen. Antibody producing EBV transformed B cells were fused with the human-mouse myeloma analogue HMMA2.11 TG/0 and six separate, stable IgM antibody producing hybridomas obtained. These results demonstrate the difficulty in obtaining human monoclonal autoantibodies, particularly of IgG isotypes, using readily accessible sources of cells in patients with chronic autoimmune diseases without expansion and preselection.

Gold lung is a hypersensitivity pneumonitis to gold-containing compounds. It can be distinguished from rheumatoid lung by its subacute or acute onset, diffuse interstitial and/or alveolar filling pattern on chest roentgenogram, presence of lymphocytes on BAL with an inverse helper/suppressor ratio, and response to withdrawal of gold and/or corticosteroid therapy. Other in vitro assays of gold hypersensitivity using peripheral blood lymphocytes are only sporadically positive and, therefore, of limited value in making the diagnosis. Physicians prescribing organic gold compounds should elicit pulmonary complaints throughout the duration of therapy. When patients receiving gold therapy present with signs and symptoms consistent with an acute or subacute hypersensitivity pneumonitis, the gold therapy should be withheld and a diagnostic workup initiated.

Bone and joint abnormalities occur frequently in sickle cell anemia but are rare in sickle cell trait. Long bone diaphyseal infarctions are distinctly unusual in sickle cell trait. We describe a patient with AS hemoglobin and symptomatic bone infarctions in the diaphyses and metadiaphyses of the long bones of the lower extremities and in the calcaneus. In addition, this patient manifested noninflammatory synovial effusions of the knee. The bone and joint manifestations of sickle cell trait are reviewed in the context of this case.

We studied 25 patients with crystal-proven gout or roentgenographic evidence of gouty arthritis, or both, in finger joints involved with nodal osteoarthritis (OA). These patients were elderly (mean age 71.4 years), and 72% of them were receiving diuretic therapy. Roentgenographic findings, in addition to features typical of OA, included soft tissue densities (tophi), with or without calcification, large intraarticular erosions, characteristic nonmarginal cortical erosions, and periarticular osteolysis. We conclude that urate crystals mediate episodes of acute inflammation in certain patients with nodal OA. This association is noted primarily in elderly patients of both sexes, especially in those receiving diuretic therapy.

Cardiac manifestations of the mucopolysaccharidoses often include valvular regurgitation, but stenotic lesions are quite rare. This report describes a 30-year-old man with mucopolysaccharidosis type II (Hunter's syndrome) and systemic lupus erythematosus who developed severe progressive aortic stenosis and died. Autopsy examination revealed evidence of various cardiac mucopolysaccharide disease including valvular leaflets thickened and distorted with fibrocalcific nodules. A brief review of previously reported valvular disease in Hunter's syndrome and other mucopolysaccharidoses is presented. This is also the first report of a patient with both systemic lupus and a mucopolysaccharidosis.

We reviewed crystal-proved gouty arthritis in 23 women. Twenty-one (91%) developed gout after menopause onset. Tophaceous gout occurred in six (26%), polyarticular involvement in 13 (57%); 70% manifested an underlying arthropathy, usually osteoarthritis. We studied 75 men with crystal-proved gout for comparison. Women developed gout significantly later compared with men, more often were receiving diuretics before gout onset, and more frequently manifested renal insufficiency and monoarticular involvement. These differences were significant when controlled for the women's later age at onset. Significantly more men than women had alcoholism and an identifiable precipitating event for acute attacks. There were no significant differences in race, age, family history of gout, disease duration, hypertension, distribution of joint involvement, tophi, or mean serum urate concentration. Gout in women is overwhelmingly postmenopausal, apparently associated with diuretic therapy and renal insufficiency independent of the effects of age. Articular characteristics in men and women are remarkably similar.

Reflex sympathetic dystrophy following a nail unit biopsy in a patient with long-standing, mycologically negative onychomycosis is reported. The significance of this complication is discussed, and the literature on the condition itself is reviewed. It is suggested that although adverse effects occur as a result of nail biopsy, they are infrequent and therefore should not dissuade the clinician from performing the procedure. Biopsy is necessary in order to establish a more accurate diagnosis of nail disease and thus administer more appropriate and effective therapy.

Extraspinal skeletal changes in diffuse idiopathic skeletal hyperostosis (DISH) consist of bony proliferation at ligamentous and tendinous insertions. We describe a patient with DISH who manifested ossific changes in the plantar fascia and peroneus longus tendon bilaterally at sites not immediately adjacent to the bony insertions of these structures. This observation expands the roentgenographic spectrum of DISH.

We describe 2 patients with progressive systemic sclerosis (PSS) who manifested characteristic pathologic abnormalities in the urinary bladder. Increased connective tissue deposition in the lamina propria and between smooth muscle bundles was demonstrated in both patients and endovascular proliferation in small arteries of the bladder was noted in one patient. Both patients had persistent unexplained microscopic hematuria; one patient manifested urinary frequency and incontinence. The relationship of these clinical abnormalities to the pathologic findings in the bladder is unclear. Structural or functional abnormalities of the urinary bladder may develop in patients with PSS.

A young black woman with systemic lupus erythematosus (SLE) who developed acute gouty arthritis of her great toe is described. The association of these 2 rheumatic diseases has been rarely reported. Factors that may be responsible for the unusual coexistence of SLE and gout are discussed. Crystal-associated arthritis should be considered in the differential diagnosis of acute oligoarthritis in SLE.

The overwhelming majority of patients with PSS present with combinations of Raynaud's phenomenon, sclerodactyly, polyarthralgias, or swelling of an extremity. However, the clinical presentation of PSS may be atypical; 14% of patients in the present series initially sought medical attention for symptoms other than Raynaud's phenomenon, tight skin, or joint pain. In the present series, only 31% of patients fulfilled the ARA criteria for PSS at the time of initial medical evaluation. Most patients manifested advanced disease by the time the criteria were fulfilled. The ARA criteria for the classification of PSS appear to have limited value with regard to making the diagnosis in an individual patient. Rapidly progressive PSS occurred in 17.6% of patients in this series and represents a particularly fulminant form of the disease whose course may not be predictable on clinical grounds at the time of initial medical evaluation or diagnosis. Patients destined to develop renal or cardiorespiratory failure usually do so in the first 3 years of disease. Close observation of PSS patients during the first 12 to 18 months may serve to identify those individuals who will undergo an accelerated disease course. Prognosis for patients with rapidly progressive PSS is poor and is associated with significantly higher mortality compared with patients with a more protracted disease course. Future therapeutic trials in PSS should be designed with the recognition that a subgroup of patients with this disorder will have a rapidly progressive disease course.

In vivo capillary microscopic findings and proximal nail fold biopsy specimens from 19 patients with various connective tissue diseases, idiopathic Raynaud's phenomenon, and non-connective tissue diseases were studied. Periodic acid-Schiff-positive serous cuticular deposits were not specific to the group of patients with connective tissue disease. Generally, the severity of deposits correlated with the severity of the in vivo capillary microscopic pattern but not with disease severity or duration. The finding of these cuticular deposits may help to identify those patients with idiopathic Raynaud's phenomenon who are at risk to develop a connective tissue disease.

Five men with progressive systemic sclerosis presented with impotence as a significant initial feature of their disease. Endocrine, urologic, and psychiatric evaluations failed to reveal another cause for impotence. We suggest that male erectile dysfunction represents another manifestation of systemic sclerosis. Possible mechanisms for this phenomenon are discussed.

Two-dimensional echocardiographic findings of subaortic fibrous ridging, aortic leaflet thickening, and aortic root dilatation and thickening are described in a group of 36 patients with rheumatoid variant diseases. The group consisted of 25 patients with ankylosing spondylitis, nine patients with Reiter's syndrome, and two patients with inflammatory bowel disease and spondylitis. No patient had clinical or laboratory evidence of aortic regurgitation or heart block. Subaortic fibrous ridging or marked leaflet thickening was noted in 11 of 36 patients; in contrast, no such changes were found in an age-matched control group of 29 men. The subgroup of patients with subaortic fibrous ridging or leaflet thickening (11 patients) had significantly longer disease duration (28.1 versus 17.7 years) and higher incidence of aortic root echo-density (82 versus 36 percent) than the remaining patients. It is concluded that a significant portion of patients with ankylosing spondylitis or Reiter's syndrome have echocardiographic evidence of aortic root involvement prior to the clinical onset of aortic regurgitation.

Combined medical and surgical treatment of a chronic lower extremity ulcer in a patient with systemic scleroderma is described. Recent pharmacological advances including calcium channel blockers, meticulous surgical care, and skin grafting offer promise for more consistent wound closure in sclerodermal skin ulcerations.