Increased levels of alternatively spliced interleukin 4 (IL-4delta2) transcripts in peripheral blood mononuclear cells from patients with systemic sclerosis.

Recent in vitro studies have shown that interleukin 4 (IL-4) induces and gamma interferon (IFN-gamma) inhibits collagen production. To define the TH1(IFN-gamma) and TH2(IL-4) cytokine profiles in systemic sclerosis (Sscl), a disease characterized by widespread fibrosis, we investigated IL-4 and IFN-gamma transcripts in peripheral blood mononuclear cells and plasma protein levels in 13 patients with Sscl. Two previously identified IL-4 transcripts, a full-length transcript and an alternatively spliced (truncated) transcript (designated IL-4delta2), were identified in patients and normal controls. Significantly increased levels of total IL-4 transcripts (full-length plus IL-4delta2 transcripts) were found in patients with Sscl in comparison to those found in healthy controls (P = 0.003), and this increase was primarily due to an increase in the level of the alternatively spliced IL-4delta2 form. The IL-4delta2/full-length-IL-4 transcript ratio was significantly increased in Sscl patients (P < 0.0001, versus healthy controls). Sequencing analysis revealed that the frequency of IL-4 clones carrying the IL-4delta2 transcript was also substantially increased in patients with Sscl. Plasma IL-4 protein levels were increased in Sscl patients compared to those in healthy controls (P = 0.001) and correlated with total IL-4 transcript levels. The up-regulation of the fibrogenic IL-4 (a TH2 cytokine) in Sscl suggests a pathogenic role for IL-4 in this disease.

Relapsing cutaneous polyarteritis nodosa associated with streptococcal infections.

BACKGROUND: Polyarteritis nodosa is an aggressive, often fatal form of vasculitis associated with multi-organ involvement. Cutaneous polyarteritis nodosa is purported to be a more benign form of this disorder with involvement limited to the skin. METHODS: The identification of a female patient from childhood to adulthood documenting repeated episodes of cutaneous polyarteritis nodosa following bouts of recurrent streptococcal pharyngitis. RESULTS: Repeated bouts of streptococcal pharyngitis at ages 11, 28, and 33 years were followed by episodes of cutaneous polyarteritis nodosa, documented by histopathologic skin changes and clinical presentation, and confirmed by therapeutic management. CONCLUSIONS: Various infectious and non-infectious conditions have been linked both to the initiation and relapse of this disease. We describe a patient with recurrent episodes of cutaneous polyarteritis nodosa spanning a period of over 20 years with each episode appearing to be linked to a prior streptococcal infection.

Granulomatous tenosynovitis: a rare musculoskeletal manifestation of tuberculosis.

A patient with tenosynovial tuberculosis affecting the extensor tendons of the wrist and hand is presented. This case highlights the clinical and magnetic resonance features of tuberculous tenosynovitis, and seeks to increase awareness of what may represent a resurgent musculoskeletal entity.

Multi-vessel biopsy-proven giant cell arteritis involving the occipital and temporal arteries.

Occipital neuralgia is a commonly encountered presenting feature in patients with giant cell arteritis. However, actual histopathologic confirmation of vasculitis of the occipital arteries is rarely cited. We present the first case of multi-vessel giant cell arteritis diagnosed with simultaneous biopsies of the right occipital and bilateral temporal arteries, along with a discussion concerning a possible role for occipital artery biopsies in the evaluation of giant cell arteritis.

Insulin-like growth factor-I is partially responsible for fibroblast proliferation induced by bronchoalveolar lavage fluid from patients with systemic sclerosis.

1. Interstitial lung disease is a common complication of systemic sclerosis. The mechanism by which excess collagen is deposited in the lung is poorly understood, but is thought to involve release of mediators which activate lung fibroblasts. In this study we investigated and partially characterized the fibroblast proliferative activity of bronchoalveolar lavage fluid from 29 patients with systemic sclerosis, 19 with and 10 without evidence of lung disease assessed by thin-section computed tomography. 2. Bronchoalveolar lavage fluid from both groups of patients stimulated fibroblast proliferation compared with control subjects: systemic sclerosis with normal computed tomography, 27.7 (range 10.5-57.9)% above control; systemic sclerosis with abnormal computed tomography, 26.7 (range 5.0-47.8)% above control, P < 0.02 in both cases. 3. The activity was reduced by about one-third by neutralizing antibodies to insulin-like growth factor-1 but not platelet-derived growth factor. Levels of insulin-like growth factor-1 of bronchoalveolar fluid were increased in patients with systemic sclerosis [2.10 (range 1.10-3.48) ng/ml of bronchoalveolar lavage fluid] compared with controls [1.45 (range 1.10-2.05) ng/ml; P < 0.01]. When patients were subdivided into those with abnormal computed tomography [2.10 (range 1.20-3.48) ng/ml] and those with normal computed tomography [1.85 (range 1.10-2.90) ng/ml] only the values for the group with evidence of lung disease were increased compared with control subjects (P < 0.02). Platelet-derived growth factor could not be detected in bronchoalveolar lavage fluid from any group. Fractionation of bronchoalveolar lavage fluid demonstrated activity in several fractions consistent with the molecular masses of insulin-like growth factor-1 associated with binding proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Structural features of interstitial lung disease in systemic sclerosis.

Most studies of lung histology in systemic sclerosis have been based on autopsy specimens and consequently emphasize end-stage fibrotic disease. Although occasional pathologic descriptions of open-lung biopsies have recognized the presence of inflammatory cells, suggesting a similarity to "lone" cryptogenic fibrosing alveolitis, the two conditions have never been formally compared. In this study we describe the morphologic features of 49 open-lung biopsies from 34 systemic sclerosis patients with interstitial lung disease, many of whom had their lung disease diagnosed at an early stage. None had pulmonary hypertension. Examination of lung tissue by light microscopy showed the earliest changes to include patchy lymphocyte and plasma cell infiltration of the alveolar walls, interstitial fibrosis, and increased macrophages but only occasional polymorphonuclear cells and lymphocytes in the alveolar spaces. Alveolitis was not observed without fibrosis. Comparison of 22 biopsies with a similar number from patients with lone cryptogenic fibrosing alveolitis, matched for age and sex, revealed no qualitative or quantitative differences, other than a higher prevalence of focal lymphoid hyperplasia (follicular bronchiolitis) in the systemic sclerosis patients than in the lone cryptogenic fibrosing alveolitis controls (23 and 5%, respectively). There was an inverse correlation between the extent of interstitial inflammation and patients' age (p less than 0.05), disease duration (p less than 0.05), and age at onset of systemic sclerosis (p less than 0.01). There was also an inverse correlation between DLCO and interstitial fibrosis (p less than 0.01) and loss of lung architecture (p less than 0.05). Ultrastructural studies of eight systemic sclerosis biopsies showed evidence of endothelial and epithelial injury together with interstitial edema and excess collagen deposition. Occasional mast cells were observed, often in close contact with interstitial fibroblasts, but there were no tubuloreticular structures or evidence of immune complexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Pneumococcal soft-tissue infections: possible association with connective tissue diseases.

Streptococcus pneumoniae is not a well-recognized cause of soft-tissue infections. In less than 4 years, 12 cases of pneumococcal soft-tissue infection were identified through discussions with infections disease subspecialists in the Philadelphia area. Principal sites of involvement included skin and fascia, tongue, epiglottis, thyroid, brain, and breast. Pneumococcal bacteremia was documented in six cases (50%); in three of these, pneumococci were also cultured from the involved soft tissues. In the cases in which bacteremia was not demonstrated, pneumococci were isolated from the infected sites. Six patients had connective tissue diseases, of which five were diagnosed as systemic lupus erythematosus. Four of these patients were receiving corticosteroids when their infections developed. Two additional patients were HIV-seropositive intravenous drug users. S. pneumoniae may be a more important cause of soft-tissue infections than previously appreciated, especially in patients with connective tissue diseases.

Diagnosis of traumatic myositis of the intrinsic muscles of the hand by the use of three-phase skeletal scintigraphy.

A case of traumatic myositis of the intrinsic muscles of the hand is presented. This is believed to be the first report in which the diagnosis of this type of soft tissue injury was made based upon phases I and II of a three-phase bone scan. An incorrect diagnosis of primary skeletal injury could have been made if delayed, 3-4 hour (phase III) imaging alone had been performed because there was augmented uptake of tracer in the normal bone adjacent to the area of soft tissue hyperemia. This report emphasizes the need to perform three-phase scintigraphy to diagnose nonskeletal injury in patients with suspected bone trauma or pain of unknown etiology.

Recurrent septic arthritis and Milroy's disease.

Milroy's disease is a rare disorder characterized by multiple physical anomalies, the most prominent of which is lymphedema of one or both lower extremities. We describe, with a review of proposed pathogenetic mechanisms, a patient with Milroy's disease who, over a 13-year period, manifested at least 14 isolated episodes of septic arthritis of the left knee. Recurrent septic arthritis associated with Milroy's disease has not been reported previously.

Serum amylase and macroamylase in patients with systemic lupus erythematosus.

We measured serum amylase and macroamylase activity in 25 patients with systemic lupus erythematosus (SLE) and 15 controls. The mean (+/- SD) for SLE was greater than for the controls (161 +/- 71.8 versus 116 +/- 38.8 units/dl). Five patients (20%) had elevated amylase and 6 (25%) had a macroamylase present. None of the controls had amylase elevation or macroamylase. None of the patients had abdominal pain and there was no observable correlation of amylase activity with disease activity, drugs, or renal function. Elevation of serum amylase in SLE without pancreatitis is frequent, as is the presence of macroamylase. Autoantibodies to this serum enzyme may be frequent in SLE.

Chronic meningococcal meningitis. An association with C5 deficiency.

A 44-year-old man with a history of presumed meningococcal meningitis 32 years before, presented with a three-month illness, characterized by fever, 13.5-kg (30-lb) weight loss, occipital headache, shoulder pain, and muscle weakness, which had been diagnosed as "polymyositis" and treated accordingly. Evaluation revealed meningococcal meningitis due to serogroup W135 and a C5 deficiency. Evidence for the occurrence of chronic meningococcal meningitis is described.

A database management system for residency applicant files.

An automated system for recording information pertaining to applicants to the Internal Medicine Residency Program at Temple University Hospital was developed in 1983. Major objectives were to improve recordkeeping, filing, communication with applicants, and efficiency of the review committee's process. Reports generated have permitted tracking of the applicant pool throughout the recruiting season and collection of statistics which may be compared with prior years. The capacity of the Residency Office to market the Internal Medicine Residency Program through prompt, accurate, and personal communication with each applicant has been facilitated.

Primary systemic amyloidosis with a retroperitoneal mass.

A 73-year-old black woman presented with congestive heart failure, abdominal distension and ascites. A large retroperitoneal mass was demonstrated by gray-scale abdominal ultrasonography and confirmed by laparatomy and postmortem examination. This retroperitoneal mass consisted mainly of amyloid, as demonstrated by green birifringence with alkaline Congo red staining. Resistance of this staining pattern to permanganate treatment and the absence of inflammatory disease or malignancy at autopsy suggest the diagnosis of primary systemic amyloidosis. This is the first reported case of this disease manifesting as a retroperitoneal mass.

Recurrent rhabdomyolysis as a manifestation of alcoholic myopathy. Report of a case.

A 38-year-old man experienced six severe episodes of rhabdomyolysis and two episodes of pharyngeal muscle weakness superimposed on chronic alcoholic myopathy and complicated by cardiomyopathy. A muscle biopsy specimen demonstrated sharply reduced levels of electrolytes despite normal serum values; presumably, these deficiencies were related to the pathogenesis of the recurrent rhabdomyolysis.

Subclinical liver disease in systemic lupus erythematosus.

In a detailed retrospective analysis of 81 patients with systemic lupus erythematosus (SLE), elevated serum "liver enzymes" were recorded in 45 (55%) subjects. In 9 cases, the cause was non-hepatic and in 14 cases liver dysfunction was probably drug induced. Aspirin was the most common offender. Of the remaining 22 patients, 3 had congested livers secondary to heart failure and 19 had no obvious cause for liver dysfunction other than SLE itself. Liver histology was reviewed in 7 of these 19 patients. An inflammatory infiltrate of the portal areas was seen in 5, fatty liver in one and chronic active hepatitis in one. The frequency of liver dysfunction and the associated portal inflammation support the view that subclinical liver disease is a concomitant feature of SLE.