Coexistence Of Autoimmune Diseases Research Articles

Aquaporin-4 seropositivity in a patient with coeliac disease but normal neurological examination and imaging

A 32-year-old woman presented in 2002 with a headache associated with numbness of her right arm, right side of her face and left leg. Examination was normal. Investigations revealed prolonged visual evoked responses (VER) on the right and a low vitamin B12 level. Cerebrospinal fluid (CSF) analysis and magnetic resonance imaging (MRI) of her brain and spine were normal. She was given a diagnosis of multiple sclerosis (MS) and commenced on vitamin B12 replacement. Three years later, her case was reviewed by the neurology service. She had experienced ongoing sensory disturbances, urinary dysfunction and episodic visual disturbances, consisting of blurred vision, particularly in her right eye, which would last for hours. She also experienced episodes of loss of strength of her right arm and a sensation of dragging her legs. Relevant past medical history included coeliac disease. Examination was normal. Investigations showed prolonged VERs, initially only on the right then bilateral. Somatosensory evoked potentials showed defective conduction in both lower limbs. MRI brain and spine were repeated and were normal. Oligoclonal bands in the CSF were normal. Autoimmune screen was negative. B12 and folate levels, thyroid function tests and syphilis serology were all negative. Tests for aquaporin-4 antibodies were performed twice using a cell based assay with aquaporin-4 M23 isoform and were positive. The titre was three out of four. Given her worsening VERs, with both being greater than 150 ms, her ongoing symptoms and positive aquaporin-4 antibodies, she was commenced on azathioprine. We believe that this patient’s symptoms are due to neuromyelitis optica (NMO). Therapy was initiated due to her prolonged VERs and our concerns regarding future functional visual deterioration. The patient was counseled with regard to the side effects of azathioprine but was very keen herself to commence therapy. Subjectively she feels better on treatment but there has been no change electrophysiologically. We believe that this patient is part of the evolving spectrum of NMO due to her clinical history, prolonged VERs, co-existent autoimmune disease and strongly positive aquaporin-4 antibodies. NMO is an inflammatory, demyelinating syndrome of the central nervous system with predominance of optic nerve and spinal cord involvement [1]. Aquaporin-4 antibodies were first described in 2004 [2]. The sensitivity of the aquaporin-4 antibody cell based assay ranges from 85 to 91% and the specificity is 100% [3, 4]. This patient’s symptoms were mild and her neurological examination was normal. Her symptoms were suggestive of mild transient optic neuritis and myelitis. Although her imaging has been normal thus far, it is possible that her disease may represent a milder phenotype of NMO and any radiological abnormalities present at the time of symptoms could reverse quickly leaving no appreciable abnormalities. The neurophysiological testing and the aquaporin-4 antibodies aided greatly in reaching a diagnosis in this patient and facilitating therapeutic decisions. Given the sensitivity P. H. McNamara (&) 32 Albert College Avenue, Glasnevin, Dublin 9, Ireland e-mail: pmcnamara2004@hotmail.com

Dilated Cardiomyopathy With Conduction Disease and Arrhythmia

case presentation: A 48-year-old woman presents with exertional dyspnea and recurrent syncope. One year earlier, a permanent pacemaker was placed after she complained of fatigue and was found to have high-grade atrioventricular block. Now, she has echocardiographic evidence of moderate to severe left ventricular (LV) systolic dysfunction with regional wall-motion abnormalities. Nuclear imaging is notable for heterogeneous myocardial uptake of technetium Tc99m sestamibi, and coronary angiography reveals widely patent epicardial vessels. Multiple episodes of nonsustained ventricular tachycardia (VT) are documented on continuous ECG monitoring. What are the diagnostic considerations for this patient, and what further evaluations are indicated? This patient presents with dilated cardiomyopathy (DCM) with electric instability (DCM+E), which we define as conduction disease and arrhythmia out of proportion to the severity of LV systolic dysfunction. Diverse causes can result in DCM+E and fall into general categories of inflammatory, infectious, hereditary, and infiltrative processes. Cardiac presentation associated with these conditions is distinct from more common causes of DCM such as ischemic heart disease, viral myocarditis, valvular dysfunction, pregnancy, or substance abuse. Clinical features that are suggestive of DCM+E include supraventricular arrhythmias or conduction disease that precedes cardiomyopathy, multiple VT morphologies, and features suggestive of ischemic heart disease (Q waves, regional wall-motion abnormalities, perfusion defects, ventricular aneurysm) in the absence of epicardial stenoses. In this Clinician Update, we focus on the diagnostic approach to patients with DCM+E. Emphasis is placed on diagnoses that are relatively common or for which the clinical management would be impacted significantly by recognition of the underlying cause. Ischemic heart disease may present with conduction disease and a high burden of arrhythmia, especially in the setting of acute myocardial ischemia/infarction. The exclusion of obstructive coronary artery disease is strongly recommended in patients with DCM+E because atherosclerosis is so prevalent, evidence-based treatment is readily available, and the …

Clinical aspects of sarcoidosis with autoantibodies

Among 64 sarcoidosis cases, 6 cases with autoantibodies or autoimmune disorders are described. All 6 cases were females over 40 years old, and made up 24% of the original 25 patients over 40 years old. Rheumatoid factor was observed in 2 cases, anti-DNA antibody in 4 cases and anti-microsomal antibody in 2 cases. Four cases of sarcoidosis were associated with ITP or Hashimoto's disease or rheumatoid arthritis. The presence of these autoantibodies or autoimmune diseases seemed to correlate with continued disease activity of sarcoidosis. The analysis of the clinical features of sarcoidosis with coexistent autoimmune diseases may clarify immunologic processes involved in the pathogenesis of both disorders and also provide clues to understanding the relatively poor clinical outcome of longstanding sarcoidosis.

Hepatitis C and Autoimmune Hepatitis: What Gets Treated First?

The coexistence of chronic hepatitis C (CHC) and autoimmune hepatitis (AIH) creates a clinical dilemma. Histologic features may suggest the predominance of one versus the other. Nevertheless, histologic differences are not absolute. Immunosuppressive therapy may be used as frontline treatment for patients with predominant histologic features of AIH. In the absence of clinical and biochemical improvement, interferon should not be withheld and a trial of antiviral therapy should be considered. Interferon can be frontline therapy for patients with the overlap syndrome, if histologic features of CHC predominate, a low titer of autoantibodies is present, and coexistent autoimmune diseases are absent. No matter what treatment is offered, close monitoring during the course of treatment is a necessity.

Down syndrome and coexistent autoimmune diseases

Summary Down syndrome (DS) is often accompanied by autoimmune diseases. Among those, autoimmune thyroid disease, type 1 diabetes and celiac disease are the most common. The major cause of enhanced vulnerability of DS patients to a variety of autoimmune diseases is impaired immune response, with multiple abnormalities in all components of the immune system, especially in cell-mediated immunity. This could explain a significantly higher frequency of autoimmune disorders in DS compared to the general population. The diagnosis of autoimmune diseases accompanying DS could be complicated by masking effects of the underlying features of the syndrome such as failure to thrive, short stature and delayed puberty. However, screening for immunological signs of coexistent autoimmunity such as tissuespecific antibodies and monitoring insulin secretion, glucose levels, thyroid function and other metabolic parameters should help in early diagnosis of coexistent autoimmunity in DS patiens.

Expansion of Polyclonal CD4+CD25high Foxp3+ Regulatory T-Cells in High Risk Myelodysplastic Syndromes (MDS).

Foxp3+ regulatory T-cells(Tregs) play a central role in maintaining tolerance. A reduction in Tregs activity is a key feature of autoimmune diseases, whereas their expansion in malignant diseases leads to suppression of the host anti-tumour responses. Expansion of oligoclonal cytotoxic T cells, inhibition of MDS CD34+ progenitors proliferation and response to immunosuppressive therapy suggest that autoimmunity contributes to the pathophysiology of low risk MDS. However, this is not generally a feature of high risk MDS. We hypothesise that in high risk MDS patients an increased number of Tregs may suppress immune responses against the dysplastic clone. In early MDS, these cells may be reduced and or be associated with coexistent autoimmune diseases, an uncommon but recognised association of low risk MDS. We therefore studied CD4+ CD25high Foxp3+ and CD8+ CD25+Foxp3+ Tregs in peripheral blood of MDS patients and examined correlation with bone marrow blasts, cytogenetic Status, IPSS score and progression to AML. Clonality of CD4+CD25+ Tregs was assessed by TCR spectratype analysis of CDR3 size distribution and by CDR3 sequence analysis.52 patients with MDS (30 male, 22 female) with a mean age of 62 years (range 40 to 82 years) were studied. According to WHO classification, 5/52 (10%) had a diagnosis of 5q− syndrome, 9/52(17%) refractory anaemia (RA), 18/52 (35%) refractory cytopenia with multilineage dysplasia (RCMD), 16/52 (31%) refractory anaemia with excess blasts (RAEB) and 4/52 (7%) patients MDS/MPD (one with JAK2 V617F Mutation). Cytogenetic study shows normal pattern in 57%, 5q- in 22%, stable cytogenetic in 10% and complex findings in 11%. All samples were taken at diagnosis prior to any treatment. In addition 5 samples were analyzed pre and post 5-Azacytidine therapy. The absolute number of CD4+CD25highFoxp3+ regulatory T cells in 5q- syndrome was 0.5±0.28×107/l, RA0.6±0.56×107/l, RCMD1.42±0.97×107/l, RAEB2.8±2.2×107/l and MDS/MPD 2.9±2×107/l. In cases with <5% bone marrow blasts (RA, 5q− & RCMD)absolute number and percentage of Tregs was significantly lower than those with ≥5% BM blasts (p=0.001). The mean number was also significantly lower at 0.73±0.57×107/l in low risk cases(IPSS 0) compared with 2±1.5×107/l in intermediate and high risk groups (p=0.008). CD8+ Tregs were not significantly different between the subtypes of MDS and between low and high risk IPSS subgroups. Tregs number did not differ significantly between various cytogenetic subgroups. The spectratype of CD4+CD25+ TCR amplicons, showed a polyclonal pattern and the overall complexity of Vβ subfamilies was not different between low risk and high risk MDS, suggesting that the expanded Tregs in high risk MDS are not clonal and likely to arise by peripheral expansion rather than an antigen-driven response. CD4+ CD25high Foxp3+ Tregs in five patients were studied pre and post 5-Azacytidine. The numbers were significantly decreased after treatment in the one patient who responded to treatment (p=0.001), whereas Treg numbers were unchanged or increased in non responsive cases. In 5 RCMD cases with concomitant autoimmune diseases the percentage of Tregs was lower than other patients within the same subgroup of MDS, however, this did not achieve statistical significance.The findings indicate Tregs are altered in MDS and may be important in the pathophysiology of MDS. Monitoring of Tregs numbers can be a useful indicator for disease progression and response to immunosuppressive therapy.

Collagenous colitis and lymphocytic colitis: Patient characteristics and clinical presentation

Objective. Collagenous colitis and lymphocytic colitis (collectively known as microscopic colitis) are characterized by chronic diarrhea, normal endoscopic and radiologic findings, and typical findings on histologic examination of colonic tissue. The purpose of this study was to define the background characteristics of patients with microscopic colitis, as well as to present symptoms, coexistent autoimmune diseases, and a possible association with the use of non-steroidal anti-inflammatory drugs (NSAIDs) and ticlopidine. Material and methods. A retrospective chart review was carried out on all cases of collagenous colitis and lymphocytic colitis diagnosed at a single center from July 1992 to July 2002. Results. Of the 104 patients identified, 66 had collagenous colitis, 35 had lymphocytic colitis, and 3 were diagnosed with both disorders at different times. The mean age of patients was 64 years (26–88 years), with a female:male ratio of 4.8:1. The most common presenting symptoms were diarrhea (95%), weight loss (41%), abdominal pain (40%), fecal urgency (29%), and nocturnal stools (22%). Autoimmune disease was diagnosed in 29% of patients, 35% were using an NSAID, and 2% were using ticlopidine. Conclusions. Collagenous colitis and lymphocytic colitis occur more often in females than in males, at a wide age range, with a mean in the seventh decade. Certain symptoms are characteristic, but are not specific to these disorders. There may be an association with the presence of a coexistent autoimmune disorder and the use of drugs such as NSAIDs.

Microscopic colitis: A retrospective study of clinical presentation in 53 patients

To evaluate the relationship between symptoms and microscopic colitis (MC) subtypes: to test whether collagenous colitis (CC) and/or lymphocytic colitis (LC) might be related to both constipation and diarrhea. A cohort of patients with independently confirmed typical histopathological changes was investigated. Fifty-three patients with histologically proved MC (46 with CC, 7 with LC) were included. The existence of diarrhea or constipation and the co-existence of autoimmune diseases were also investigated and all data were retrospectively analyzed. Twenty-three (43.39%) of MC patients had chronic constipation (20 in CC, 3 in LC patients). Twenty-four (45.28%) of MC patients had autoimmune disease and the diagnosis of autoimmune disease was always prior to MC. Sjögren's syndrome was associated only with the constipation subgroup. The Janus face of MC resembles the subgroups of irritable bowel syndrome. The co-existence of autoimmune diseases and MC is confirmed in both the constipation and diarrhea subgroups.

Multiple Myeloma in a Patient with Systemic Lupus Erythematosus, Myasthenia Gravis and Non-Familial Diffuse Palmoplantar Keratoderma

The coexistence of autoimmune diseases and malignancies including lymphoproliferative diseases is often reported in the literature. Here we report an unusual case with two autoimmune diseases--myasthenia gravis (MG) and systemic lupus erythematosus (SLE) associated with unique palmoplantar keratoderma (PK) which preceded the development of multiple myeloma (MM) for twenty and seven years respectively. MG associated with non-malignant thymoma developed in 1981 and was successfully treated with thymectomy and physostigmine. Thirteen years later SLE was diagnosed and until now it is also accompanied by skin lesions corresponding to non-familial, diffuse palmoplantar keratoderma which is resistant to treatment. In 2001 the patient revealed inguinal and abdominal lymphadenopathy first diagnosed as extramedullary plasmacytoma and then as multiple myeloma on the basis of bone marrow infiltration and monoclonal gammopathy. Therapy with VAD regimen achieved complete remission of the MM and significant improvement of the skin changes lasting for six months. We failed to collect sufficient numbers of CD 34+ cells for peripheral blood stem cell transplantation. Now the malignancy is in partial remission after CHOP therapy and the skin lesions have returned to their initial status. To our knowledge, this is the first case to be reported with coexistence of these four diseases.

Thymoma, thymic hyperplasia, thymectomy and autoimmune diseases (Review)

There is a bidirectional relationship between autoimmunity and cancer: on the one hand, patients with autoimmune conditions develop neoplastic diseases, and on the other hand, malignant conditions are associated with paraneoplastic autoimmune syndromes. Thymoma is an epithelial tumor which is often accompanied by autoimmune diseases: about a third of the patients with thymoma have myasthenia gravis. Pure red cell aplasia, pemphigus and systemic lupus erythematosus, might also coexist with this tumor. Thymectomy is an optional treatment in some autoimmune diseases (i.e. myasthenia gravis, multiple sclerosis, autoimmune hemolytic anemia, ulcerative colitis, and systemic lupus erythematosus). In this communication we review and discuss the coexistence of autoimmune diseases, thymoma or thymic hyperplasia, and the dual effects of thymectomy on their course.

Evaluation of Islet-Specific Autoantibodies in Japanese Patients with Insulin-Dependent Diabetes Mellitus: A Comparison between Autoantibodies to Glutamic Acid Decarboxylase, Autoantibodies to 64 kDa Islet Cell Protein and Islet Cell Antibodies

Autoantibodies to glutamic acid decarboxylase (GAD), autoantibodies to 64 kDa islet cell protein and islet cell antibodies (ICA) were measured in 79 Japanese patients with insulin-dependent diabetes mellitus (IDDM). The overall prevalences of GAD antibodies, 64K antibodies, and ICA in these patients were 69.6% (55/79), 48.1% (38/79), and 46.8% (37/79), respectively. However, in a subset of these patients with recent onset IDDM (< 1 year) the prevalences of GAD antibodies, 64K antibodies, and ICA were 78.8% (26/33), 66.7% (22/33), and 78.8% (26/33), respectively. Furthermore, the prevalences of GAD antibodies, 64K antibodies, and ICA were significantly decreased in patients with long standing diabetes at 60.9% (28/46), 34.8% (16/46), and 23.9% (11/46), respectively. However, when these patients were divided into two groups by the presence or absence of organ-specific autoimmune disease (OSAD), the mean levels of GAD antibodies and ICA in the patients who gave a positive result were significantly higher in patients with OSAD (397 units and 98 JDF units, respectively) than in patients without OSAD (74 units and 39 JDF units, respectively). These results demonstrate that it is important to evaluate the prevalences and levels of islet-specific autoantibodies when considering disease duration and co-existence of autoimmune disease in patients with IDDM.

Autoimmune thyroid phenomena are not evidence for human lymphocyte antigen-genetic heterogeneity in insulin-dependent diabetes.

It is well established that there is genetic heterogeneity between a human lymphocyte antigen (HLA)-DR3-associated allele and an HLA-DR4-associated allele in insulin-dependent diabetes mellitus (IDDM). Equally well established are the association of DR3 with Graves' disease and other autoimmune disorders in nondiabetics and the increased prevalence of autoimmune thyroid disease in IDDM. Perhaps in large part because of these facts, it has been postulated that there are two major forms of classical IDDM--one form characterized by coexistent autoimmune disease, such as autoimmune thyroid disease which is associated with DR3, and another form not associated with additional autoimmune disorders, which is associated with DR4. Several studies have repudiated the idea of specific clinical findings in IDDM being associated exclusively with DR4. However, the DR3-thyroid association in IDDM has not been investigated carefully. Therefore, in order to study this putative association, we divided a group of diabetic children into overlapping subgroups based on thyroid enlargement, antithyroid microsomal antibodies, acquired hypothyroidism, and no evidence of thyroid disease. The distributions of HLA-DR3 and -DR4 among these subgroups did not differ from each other; nor did the distribution of the HLA alleles differ from those of randomly selected IDDM individuals. These results suggest that thyroid autoimmunity in IDDM is part of the IDDM "syndrome" and is associated with DR3 and DR4 to the same extent that IDDM without thyroid disease is associated with these two antigens. Thus, although genetic studies are consistent with the heterogeneity between DR3 and DR4 in IDDM, there is no HLA-thyroid disease association to support this heterogeneity.

Autoimmune features as determinants of prognosis in steroid-treated chronic active hepatitis of uncertain etiology

To determine if autoimmune features influence the prognosis of severe sporadic chronic active hepatitis of uncertain etiology, 126 corticosteroid-treated patients who had been screened to exclude active hepatitis B infection and possible drug effects or transfusion-related disease were categorized according to the presence of the lupus erythematosus cell, antinuclear antibody, smooth muscle antibody, and coexistent autoimmune diseases. Patients with auto-immune markers had findings similar to those without these features and responses to therapy were comparable. Remission (77% vs. 68%), treatment failure (16% vs. 14%), progression to cirrhosis (31% vs. 39%), and death from hepatic failure (4% vs. 12%) occurred with similar frequency in patients with and without the lupus erythematosus cell or antinuclear antibody. Although patients with the lupus erythematosus cell or antinuclear antibody tended to relapse less frequently than others, 5-yr survival was not increased (92% vs. 87%). Autoimmune diseases occurred as commonly in patients without the lupus erythematosus cell or antinuclear antibody as in those with these findings (16% vs. 17%), and the presence of these conditions did not identify patients with a different clinical behavior. In severe sporadic chronic active hepatitis of uncertain etiology, a clinically and prognostically distinct subgroup reflective of a possible autoimmune disorder cannot be defined.

Clinical characteristics and etiological markers in insulin-dependent diabetes associated with an organ-specific autoimmune disease.

Thirty-four insulin-dependent diabetics with a coexistent organ-specific autoimmune disease (Graves' disease, primary myxedema, adrenal insufficiency, generalized vitiligo, primary biliary cirrhosis) were compared to 100 insulin-dependent patients in whom no obvious etiology was detectable. The autoimmune group was characterized by a predominance of females, a family history of autoimmune disease, a later age at onset, better glycemic control, low insulin requirement, persistence of ICA, and greater frequency of HLA B8 but not of B18. However, there was a large overlap between the two groups for all these criteria. In addition, a family history of IDD in first degree relatives and the frequency of serum positive for neutralizing anti-Coxsackie B antibodies were identical in the two groups. These results do not justify the separation of this group of patients as having purely autoimmune diabetes, to the exclusion of other etiological factors, whether genetic or viral.

EVIDENCE FOR RAISED K-CELL LEVELS IN TYPE-I DIABETES

The proportion of blood mononuclear cells forming low-affinity rosettes with sheep erythrocytes (K cells) was abnormally high in 13 (57%) of 23 children with classical type-1 diabetes at diagnosis but normal in children who had had diabetes for more than a year. A raised proportion of K cells was also found in 5 out of 10 unaffected siblings with islet-cell antibodies and at least one HLA haplotype in common with the diabetic proband; and in 10 (45%) of 22 subjects with type-1 diabetes and co-existent autoimmune thyroid disease irrespective of the duration of diabetes or the presence of islet-cell antibodies. These findings may be new evidence for lymphocyte-mediated β-cell destruction and support the idea of immuno-genetic heterogeneity within type-1 diabetes.

Pancreatic Islet-cell Antibodies in Diabetes Mellitus Correlated with the Duration and Type of Diabetes, Coexistent Autoimmune Disease, and HLA Type

In a study of 972 patients with diabetes mellitus, humoral pancreatic islet-cell antibodies (I.C.Ab.) were detected in highest prevalence in insulin-treated diabetics with (38 per cent) and without (22 per cent) associated overt organ-specific autoimmune disease (A.I.D.) where consideration was not given to the duration of diabetes. They were also detected in 8 per cent of diabetics treated with oral hypoglycemic agents (O.H.A.), but not in diabetics requiring diet alone and in only 0.5 per cent of 434 control subjects. Six per cent of 522 patients with overt organ-specific A.I.D. but not diagnosed to be diabetic had I.C.Ab.s. I.C.Ab.s were present in the sera of 2 per cent of 157 first-degree relatives of I.C.Ab.-positive subjects. In insulin-treated diabetics and, to a lesser extent, in diabetics not requiring insulin, the prevalence of humoral I.C.Ab. was strongly dependent of the duration of the diabetes, being 60 per cent during the first year from diagnosis in the insulin-treated group and falling to 20 per cent at two to five years and to 5 per cent at 10-20 years. The prevalence of I.C.Ab. in insulin-treated diabetics showed no correlation with the patient's age at the time of testing when the duration of diabetes was taken into account. Diabetics who did not require insulin for treatment but who were I.C.Ab.-positive showed a significant tendency to subsequently require insulin and to have a higher prevalence of other autoantibodies than insulin-independent diabetics who were I.C.Ab.-negative. Persistence of I.C.Ab. for more than five years from diagnosis of diabetes was associated with coexistent overt organ-specific A.I.D. and with HLA-B8, A1, and A1 + B8.

Pancreatic islet-cell antibodies in diabetes mellitus correlated with the duration and type of diabetes, coexistent autoimmune disease, and HLA type

Pancreatic islet-cell antibodies in diabetes mellitus correlated with the duration and type of diabetes, coexistent autoimmune disease, and HLA type

RELAPSING POLYCHONDRITIS

Relapsing polychondritis (RP) is not a totally rare rheumatic disease. We have seen 23 patients from 1960-1975, and there are now a total of 159 reported cases, which form the basis of this study. RP occurs equally in both sexes, and has a maximum frequency in the fourth decade. 2) Empirically defined diagnostic criteria are proposed, to include the most common clinical features: a) Bilateral auricular chondritis b) Nonerosive sero-negative inflammatory polyarthritis c) nasal chondritis d) Ocular inflammation e) Respiratory tract chondritis f) Audiovestibular damage The diagnosis is based primarly upon the unique clinical features, and is quite certain if three or more criteria are present together with histologic confirmation. 3) Fifty percent of patients present with either auricular chondritis or the arthropathy of RP; but with prolonged follow-up, a majority of patients develop four or more of the above mentioned criteria. 4) Approximately 30 percent of patients have a preceding or coexistent rheumatic or autoimmune disease, which can lead to initial diagnostic confusion. 5) Laboratory and radiographic investigations help mainly to rule out other diagnostic possibilities, with no characteristic abnormalities being present in a majority of patients. 6) On follow-up, three-fourths of our patients required chronic corticosteroid therapy with an average dose of 25 mg per day of prednisone. Corticosteroids decrease the frequency, duration, and severity of flares, but do not stop disease progression in severe cases. 7) The mortality rate has been 30 percent in our series and 22 percent in the other 136 reported cases. Of the 29 cases where the cause of death was known, 17 were from respiratory tract involvement and 9 from cardiac valvular or vasculitic involvement, emphasizing the need to search for critical involvement of either of these organ systems in each patient. 8) Detailed reports of selected cases are presented to illustrate the clinical diagnosis and differential diagnosis, and to demonstrate the need for careful prolonged follow-up. 9) Although the etiology remains unknown, there is a frequent association with, and clinical similarity to, other rheumatic diseases. 10) Careful clinicopathological study of our 23 patients leads us to postulate an underying systemic vascultis as an important pathologic mechanism in RP.