Questionnaire survey on the prevention and development of cervical cancer in patients with systemic lupus erythematosus in Japan.

OBJECTIVES: The aim is to evaluate the prevention and development of cervical cancer in systemic lupus erythematosus (SLE) patients in Japan and its background based on a questionnaire survey. METHODS: The questionnaire was handed to 460 adult female SLE patients at 12 medical institutions. The participants were grouped by age, and data related to their human papillomavirus vaccination status, age at first coitus, cervical cancer screening, and diagnosis of cervical cancer were analysed. RESULTS: A total of 320 responses were received. Patients aged 35-54 years included a higher proportion of patients whose age at first coitus was <20 years. This group also showed a higher rate of cervical cancer/dysplasia. Only nine patients had a human papillomavirus vaccination history. Adequate frequency of cervical cancer screening was slightly higher (52.1%) among SLE patients than in the Japanese general population. However, 23% of the patients had never undergone examination, primarily because of a feeling of troublesome. The incidence of cervical cancer was significantly higher among SLE patients. One reason for this may be associated with the use of immunosuppressants, although the difference was not significant. CONCLUSIONS: SLE patients are at a higher risk of cervical cancer and dysplasia. Rheumatologists should proactively recommend vaccination and screening examinations for SLE female patients.

Scleroderma renal crisis during intravenous cyclophosphamide pulse therapy for complicated interstitial lung disease was successfully treated with angiotensin converting enzyme inhibitor and plasma exchange.

Systemic sclerosis (SSc) is a multiorgan disorder involving the skin, heart, lungs, kidneys, and intestines. Progressive interstitial lung disease (ILD) is a serious complication in SSc patients, and cyclophosphamide (CYC) is the only recommended therapy for this condition;(1)) however, its clinical effectiveness is not sufficient. Scleroderma renal crisis (SRC) is a rare complication, characterized by acute renal failure and progressive hypertension. Angiotensin-converting-enzyme inhibitor (ACE-i) is a widely accepted therapy for SRC. We report an SSc patient with SRC and progressive ILD who underwent treatment with CYC and successful treatment with ACE-i and plasma exchange (PE). SRC and ILD are significant contributors to morbidity and mortality among SSc patients, and the therapy for these disorders is of great interest to rheumatologists. This study presents the possibility of favorable effects of PE for SSc-associated ILD and SRC.

A case of ureteral stenosis due to ureteritis probably associated with rheumatoid arthritis.

Ureteritis associated with the immunological disorder is rarely reported, and most cases in this category are small vessel vasculitis and immunoglobulin G4-related disease. Rheumatoid arthritis (RA)-associated ureteritis is uncommon, and underlying aetiology is unclear. We present a patient with ureteritis who had a medical history of RA and was successfully treated with steroids and immunosuppressant. A 49-year-old woman who had been treated for RA and atopic dermatitis suffered from gross haematuria for 5 successive days. Contrast-enhanced computed tomography (CT) showed right-dominant upper urinary tract dilatation with enhanced thickened wall. The haematuria continued accompanied with intermittent right back and lower abdominal pain, and the following CT image taken after 3 months presented the progression to bilateral hydronephrosis. Ureteral stents were placed, and antibiotic therapy was introduced for obstructive pyelonephritis. Ureterocystoscopy and following biopsy from the upper ureteral tract showed a chronic inflammatory change in the histopathology, and we finally considered the stenosing ureteritis to be caused by immune-mediated mechanism related to RA. After starting steroid therapy with methotrexate, therapeutic response was obtained to remove the stents. In the cases of ureteritis or ureteral stenosis of unknown aetiology with a medical history of immunological disorders, we should consider the underlying immune-activated state and try to test contrast-enhanced CT and histological examination before performing a surgical procedure. After excluding the common causes of ureteritis or ureteral stenosis, these tests would support the appropriate diagnosis.

Anti-interferon-gamma autoantibody related disseminated nontuberculous mycobacteriosis with pathological features of immunoglobulin G4-related disease.

A 72-year-old man who was diagnosed as pulmonary mycobacterium avium complex (MAC) disease had suffered from antibiotics resistant fever with left renal enlargement surrounded by inflammatory change and multiple osteolytic lesions on computed tomography (CT). The renal biopsied samples pathologically showed immunoglobulin G4 (IgG4) positive plasma cell infiltration and many acid-fast bacilli without granuloma formation. Nucleic acid identification test for MAC from the samples of vertebral osteolytic lesion was positive. In the autopsy samples from left kidney, epithelioid cell granuloma and Langhans giant cell with many acid-fast bacilli were shown pathologically. In addition to osteolytic lesions on CT study, these pathological findings were not consistent with IgG4-related disease (IgG4-RD). The diagnosis of disseminated nontuberculous mycobacteriosis was made, and plasma anti-interferon-gamma (IFN-γ) autoantibody was found as the cause of underlying immunodeficiency. Disturbed function of IFN-γ resulted in impaired ability of phagocytic cells against pathogens and leading to spread of infection. T-helper type 2 dominant immune response was induced by prolonged antigenic stimulation of mycobacteria, which might have contributed to form the pathological features of IgG4-RD.

Steroid Resistant Hypereosinophilic Syndrome Suspected to Be Caused by Aberrant T-cell Subset.

A 53-year-old male presented with cough, skin rash and lymphadenopathies complicated with hypereosinophilia (HE) in the blood, and patchy shadows in both lungs on chest computed tomography. Reactive causes for HE were excluded, and no clinical or laboratory features of myeloproliferative disorders could be found. HE caused by aberrant T-cell subsets was suspected because of serum hyper-immunoglobulin E level, and organ involvement of skin and lungs, though we could show neither aberrant T-cell surface markers nor T-cell receptor gene rearrangement. In the course of steroid monotherapy, tolerable maintenance dose could not be attained and the steroid-sparing agents of hydroxycarbamide, cyclosporine and interferon-α were introduced. However, the therapeutic response was inadequate, and organ involvement of lungs and intestinal tract developed. HE caused by aberrant T-cell subsets has steroid resistance and a risk of malignant transition, and we considered this progressive steroid refractoriness to be a sign of such a transition. Cytotoxic chemotherapy or bone marrow transplantation will likely be the next treatment modality in this patient.

Segmental Arterial Mediolysis with Preceding Symptoms Resembling Viral Infection Hampers the Differentiation from Polyarteritis Nodosa.

A middle-aged man presented with a fever, arthralgia, gastrointestinal symptoms, headache, and rash. After two weeks, the patient suddenly complained of severe abdominal pain, and computed tomography revealed aneurysms in the hepatic and splenic arteries, which increased in size progressively. Given the elevated levels of inflammatory markers and orchitis, polyarteritis nodosa (PN) was initially suspected. Catheter embolization for the ruptured hepatic aneurysm and splenectomy for the large splenic ones were performed, and the pathological finding was consistent with segmental arterial mediolysis (SAM). Changes in inflammatory marker levels and aneurysmal size are also informative to differentiate SAM from PN.

Hepatitis associated with hypereosinophilia suspected to be caused by HES that also presented with the pathological features of IgG4-related disease.

A 52-year-old woman presented to our hospital due to elevated liver enzyme levels and hypereosinophilia. Liver biopsy specimens revealed chronic hepatitis with abundant eosinophils and immunoglobulin G4(IgG4)-positive plasma cell infiltration. Systemic lymphadenopathy, including that involving the hepatic hilar lymph nodes, was observed on computed tomography, and the cervical lymph node biopsy specimens exhibited lymphoid follicular hyperplasia and IgG4-positive plasma cell infiltration. It is sometimes difficult to distinguish hypereosinophilic syndrome (HES) from IgG4-related disease, as some of the clinical findings overlap. The numerous areas of eosinophilic infiltration observed in the liver indicated a diagnosis of HES in our case.

Significance of an epidermal growth factor receptor mutation in cerebrospinal fluid for carcinomatous meningitis.

We report a case of epidermal growth factor receptor (EGFR) inhibitor-sensitive lung adenocarcinoma with carcinomatous meningitis who showed a good response to gefitinib, an oral tyrosine kinase inhibitor of EGFR. This good response to gefitinib treatment was attributed to evidence of an EGFR mutation, L858R in exon 21, which was detected in a small amount of cerebrospinal fluid (CSF) before the positive CSF cytology. Patients with carcinomatous meningitis often have a poor performance status, and therefore diagnostic approaches and therapeutic methods are also often limited. Detection of EGFR mutations may be a useful method for non-small cell lung cancer diagnosis, and also facilitate determination of appropriate therapeutic protocols.