Manifestation Of IgG4-related Disease Research Articles

Elevated serum IgG4 levels in diagnosis and treatment response in patients with idiopathic retroperitoneal fibrosis.

Idiopathic retroperitoneal fibrosis (iRPF) may be a manifestation of IgG4-related disease. Measuring serum IgG4 (sIgG4) may be of value in monitoring iRPF, but this has scarcely been evaluated. It is unknown if tamoxifen (TMX) affects sIgG4 levels. We performed a prospective inception cohort study of 59 patients with untreated (re)active iRPF stratified by elevated (>1.4g/L) or normal sIgG4 level. Changes in sIgG4 levels following TMX initiation and, if treatment failed, during subsequent corticosteroid (CS) treatment were analyzed. The median sIgG4 level was 1.1g/L (interquartile range (IQR) 0.4-2.2); 24 patients (40%) had elevated sIgG4 level. Patients with elevated sIgG4 tended to present with higher ESR (46 vs. 34mm/h; P=0.08) and more frequent locoregional lymphadenopathy adjacent to the mass (41.7 vs. 20.0%; P=0.08). sIgG4 also correlated with ESR (ρ=0.26; P=0.05) and serum creatinine (SC) (ρ=0.26; P=0.04). Following TMX initiation, sIgG4 level decreased, particularly when achieving treatment success (P<0.01). Odds ratio for TMX treatment success in patients with elevated sIgG4 level was 0.77 (95% CI 0.53-1.14; P=0.19). After adjusting for age, sex, and SC, the odds ratio was 0.78 (95% CI 0.51-1.18; P=0.24). ROC curve analyses of sIgG4 on a continuous scale and treatment success showed an AUC of 0.62. Treatment success and concurrent sIgG4 decrease (P<0.01) were achieved in 78% of patients who converted to CS therapy. Patients with elevated sIgG4 level may be more inflammatory than patients with normal sIgG4 level, but this needs further study. TMX affects sIgG4 levels, but to a lesser extent than CSs. sIgG4 cannot be used as an outcome prediction tool, irrespective of which cutoff value was chosen.

No definite clinical features of immunoglobulin G4–related disease in patients with pulmonary nodular lymphoid hyperplasia

Pulmonary nodular lymphoid hyperplasia (PNLH) may show heavy lymphoplasmacytic infiltrates with increased immunoglobulin G4 (IgG4)-positive plasma cells as in IgG4-related disease (IgG4-RD). However, it is unclear whether PNLH could be a manifestation of IgG4-RD. A recent study reported the presence of Epstein-Barr virus (EBV) in IgG4-related lymphadenopathy. We postulated that a subset of PNLH might represent IgG4-related lung disease with EBV-positive lymphocytes as has been reported in IgG4-related lymphadenopathy. IgG and IgG4 immunohistochemistries were performed on 26 PNLH cases in our files (1994-2014) and on 9 controls including diffuse lymphoid hyperplasia of the lung without nodularity (n=2), usual interstitial pneumonia with increased lymphoplasmacytic infiltrates (n=5), and thoracic lymphadenopathy (n=2). EBV in situ hybridization was performed in the cases with the highest IgG4+ count (n=15). Median IgG4+ plasma cell count in PNLH was 36 cells per high-power field (interquartile range, 7-65) with median IgG4+/IgG+ ratio of 0.24 (interquartile range, 0.12-0.37). Three of 26 cases had a markedly increased IgG4+ count (range, 55-139) and IgG4+/IgG+ ratio (>0.4). Serum IgG4 level available in 1 of these cases was not elevated, and all 3 patients had alternate medical diagnoses. Absolute counts of IgG4+ plasma cells in PNLH did not significantly differ from the other control groups. Result of EBV in situ hybridization was negative in all cases tested. In conclusion, most PNLH cases had low IgG4+ cells, and there was no clinical evidence of IgG4-RD or EBV among those with increased IgG4+ cells.

Autoimmune pancreatitis.

Autoimmune pancreatitis (AIP) is a rare, distinct and increasingly recognized form of pancreatitis which has autoimmune features. The international consensus diagnostic criteria (ICDC) for AIP recently described two subtypes; type 1[lymphoplasmacytic sclerosing pancreatitis (LPSP)] and type 2 [idiopathic duct-centric pancreatitis (IDCP) or AIP with granulocytic epithelial lesion (GEL)]. Type 1 is the more common form of the disease worldwide and current understanding suggests that it is a pancreatic manifestation of immunoglobulin G4-related disease (IgG4-RD). In contrast, type 2 AIP is a pancreas-specific disease not associated with IgG4 and mostly without the overt extra-pancreatic organ involvement seen in type 1. The pathogenesis of AIP is not completely understood and its clinical presentation is non-specific. It shares overlapping features with more sinister pathologies such as cancer of the pancreas, which continues to pose a diagnostic challenge for clinicians. The diagnostic criteria requires a variable combination of histopathological, imaging and serological features in the presence of typical extrapancreatic lesions and a predictable response to steroids.

Abdominal Manifestations of IgG4-Related Disease

IgG4-related disease is a recently recognized systemic disorder involving multiple organs throughout the body. The multi-organ involvement of this disease was previously thought to occur as isolated, unrelated autoimmune disorders. Although virtually any part of the body may be involved in IgG4-related disease, abdominal manifestations tend to predominate in most affected individuals. While autoimmune pancreatitis is the most commonly encountered abdominal disorder in the setting of IgG4-related disease, the liver, kidneys, gastrointestinal tract, retroperitoneum, and mesentery may likewise be involved. Various diagnostic criteria for IgG4-related disease have been proposed based on physical exam, serology, and histopathologic confirmation. However, imaging plays an essential role in the diagnosis of this disorder, not only to establish the presence of IgG4-related disease, but to assess the severity and extent of systemic disease involvement.

鼻粘膜病変を呈した IgG4 関連疾患の2例

鼻粘膜病変を呈した IgG4 関連疾患の2例

A Case Report of IgG4-Related Autoimmune Cholangitis

Introduction: Autoimmune cholangitis is a biliary manifestation of IgG4 related disease (IgG4-RD) which can affect many organs and only rarely occurs in the absence of autoimmune pancreatitis. We present a case of IgG4 related cholangitis and discuss differential diagnosis and the role of clinical, laboratory and radiologic findings in establishing the diagnosis. Methods: N/A. Results: A 66 year old man was sent to the ED from his gastroenterologist's office for 3 weeks of jaundice, lower abdominal cramping, pale yellow stools 3-4 times daily, and dark orange urine. An outpatient abdominal ultrasound showed biliary obstruction and diffuse thickening of the common duct. In the ED, the patient appeared jaundiced but hemodynamically stable. Laboratory studies showed total bilirubin 11, direct bilirubin 8.9, AST 60, ALT 45, ALKP 265, amylase 65, and lipase 278. MRCP showed proximal and distal common bile duct strictures with intrahepatic and common duct dilation, circumferential biliary hyperenhancement, and bilateral striated heterogeneous nephrograms. The combination of these findings suggested the possibility of autoimmune cholangitis. ERCP was not initially performed due the location of the more proximal stricture and the possible risk of bacterial seeding of an obstructed biliary system. IgG4 levels were drawn and the patient was discharged on prednisone 40mg daily. Total IgG level and IgG4 returned elevated at 2641 and 459, respectively. Antinuclear antibody and anti-smooth muscle antibody were negative. After 2 weeks of steroid therapy, total bilirubin decreased to 2.4. Conclusion: IgG4 associated cholangitis was first described in the literature in 1995 and since then, there have been only a few case reports. IAC can further be classified into type 1 or 2; type 1 stenosis is exclusively located in the distal CBD, whereas type 2 stenosis is affects intra- and extrahepatic bile ducts. Diagnosis of biliary strictures with painless jaundice is also concerning for cholangiocarcinoma and pancreatic neoplasm, and these should be ruled out in the process of working up for an autoimmune cause. Steroid therapy is the initial treatment modality and many patients have good response. Changes in LFTs are best seen 5 and 10 days after therapy initiation and earlier initiation of therapy reduces risk of biliary cirrhosis. This case highlights the importance of laboratory and radiologic data in obtaining an accurate diagnosis.

Autoimmune Pancreatitis: A Diagnostic Challenge for the Clinician.

Autoimmune pancreatitis (AIP) is a rare cause of chronic pancreatitis that poses a diagnostic challenge to the clinician in that it mimics pancreatic cancer and presents with painless obstructive jaundice. In this review, we discuss the two types of AIP: type 1, known as lymphoplasmacytic sclerosing pancreatitis and type 2, known as idiopathic duct centric pancreatitis. Type 1 AIP is considered as a pancreatic manifestation of immunoglobulin G4-related disease. The etiopathogenesis of AIP, particularly type 2 AIP, is largely unknown. Both types of AIP have unique pancreatic histological features; however, the radiological and clinical features may mimic those of pancreatic cancer. The most commonly used diagnostic criteria, including the Japan Pancreas Society criteria, the Mayo Clinic HISORt (histology, imaging serology, other organ involvement, and response to therapy) criteria, and the International Association of Pancreatology's international consensus diagnostic criteria, that help to differentiate AIP from pancreatic cancer are reviewed in this article. The treatment of choice for induction of remission for AIP is steroid therapy. Relapses are more common in type 1 AIP. In selected patients, immunomodulators such as azathioprine and rituximab are used to maintain remission.

Are plasma cell-rich inflammatory conditions of the oral mucosa manifestations of IgG4-related disease?

AimThe aim of this study was to characterise plasma cell infiltrates, in terms of IgG4 positivity, in specific and non-specific plasma cell-rich chronic inflammatory conditions of the oral mucosa. Exploring...

IgG4 related disease of the head and neck.

IgG4 related disease of the head and neck region represents one of the more common manifestations of IgG4 related disease. Involvement of the submandibular and parotid glands, the orbit and thyroid represent some of the more common sites involved by IgG4 related disease. Eosinophilic angiocentric fibrosis, Mikulicz disease and Riedel thyroiditis are also members of the family of IgG4 related disease. Clinically, the disease is characterized by tumefactive lesions, often multicentric, that show a swift response to immunosuppressive therapy. An elevated serum IgG4 represents the only validated blood based biomarker. However, elevated serum IgG4 is detected in only half the patients with this disease. Histology continues to represent the gold standard for the diagnosis of IgG4 related disease: storiform-type fibrosis and obliterative phlebitis constitute characteristic features of this disease. A definitive diagnosis of IgG4 related disease also requires the presence of elevated numbers of IgG4 positive plasma cells as well as an IgG4 to IgG ratio of greater than 40 %. In isolation, elevated numbers of IgG4 positive plasma cells represents a non-specific feature, detected in a variety of other inflammatory as well as neoplastic diseases. Attention to the clinical context, histological features, as well as an elevated IgG4 to IgG ratio is critical to avoiding overdiagnosis of IgG4 related disease.

IgG4-related pleural disease

IgG4-related disease (IgG4-RD) is a newly recognized chronic systemic fibroinflammatory disease that displays protean manifestations. Since the initial description of IgG4-related pancreatitis (type 1 autoimmune pancreatitis), it has become clear that IgG4-RD can involve virtually any organ in the human body including intrathoracic structures. It is characterized by infiltration of IgG4-positive plasma cells and fibrosis in affected organs. IgG4-RD affects mainly adults, more commonly men. Most commonly described form of pulmonary involvement is focal parenchymal opacities. However, other forms of parenchymal involvement such as diffuse interstitial infiltrates have been reported as well as airway, vascular, mediastinal, and pleural disease. Pleural disease in IgG4-RD can present as pleural mass, pleuritis with fibrosis, or pleural effusion. IgG4-related pleural disease can present with or without concomitant parenchymal lung lesions or extrapulmonary manifestations of IgG4-RD. In patients presenting with fibroinflammatory disease involving the pleura of obscure cause, possible role of IgG-RD should be considered.

Dermatologic disorders in 118 patients with autoimmune (immunoglobulin G4-related) pancreatitis: a retrospective cohort analysis.

Autoimmune pancreatitis is the prototypical manifestation of immunoglobulin G4-related disease, a fibroinflammatory syndrome that can affect virtually any organ. Rarely, skin involvement has been reported in immunoglobulin G4-related disease. Isolated case reports have described other distinct associated dermatoses. Our objective was to determine the frequency and nature of dermatologic manifestations of immunoglobulin G4-related disease in patients with autoimmune pancreatitis. Retrospective analysis of dermatologic conditions of patients with autoimmune pancreatitis. Among the 118 identified patients, 31 (26.3%) had a dermatologic diagnosis [mean (standard deviation; SD) follow-up 5.9 (4.6) years]. Two patients (1.7%) had necrobiotic xanthogranuloma; three (2.5%) had another xanthomatous or xanthogranulomatous process. One patient (0.8%) had pemphigus erythematosus. No patient had immunoglobulin G4-related skin disease. Skin involvement in immunoglobulin G4-related disease appears to be rare. A disproportionately high number of patients had xanthomatous or xanthogranulomatous processes, including necrobiotic xanthogranuloma. It remains unclear whether the association between immunoglobulin G4-related disease and necrobiotic xanthogranuloma or other xantho(granulo)matous processes represents shared pathophysiology, a mutual underlying driver, or coincidence, though the results of this study cast doubt on the latter. Although pemphigus was not reported in immunoglobulin G4-related disease previously, the prominent role of the immunoglobulin G4 subclass in each condition makes this association intriguing.

Paquimeningitis hipertrófica secundaria a enfermedad relacionada con IgG4: descripción de un caso y revisión de la bibliografía

Hypertrophic pachymeningitis is an infrequent disorder that produces focal or diffuse thickening of the dura mater. It can be idiopathic or secondary to infectious, autoimmune or neoplastic processes. The recently described 'IgG4-related disease' could be the cause of many cases considered cryptogenic. A 54-year-old woman, with a history of bronchial asthma, presented with headache, dizziness and hearing loss on her left ear. The brain MRI study with gadolinium showed enhancement and thickening of the dura mater, extending from lateral wall of left cavernous sinus and medial temporal lobe to cerebellopontine angle and ipsilateral tentorium. CSF had 10 leukocytes/µL (90% mononuclear), with 1 g/L protein and without glucose consumption. Pathology showed fibrosis and lymphoplasmacytic infiltrate, with 16 IgG4+ plasma cells per high power field. The rest of analytical and microbiological studies were normal or negative. The plasma IgG4 rate was within normal limits. After treatment with steroids there was clinical improvement accompanied by the virtual disappearance of the alterations detected in neuroimaging. Hypertrophic pachymeningitis as a manifestation of IgG4-related disease can be diagnosed based on MRI findings if plasma IgG4 is elevated. In doubtful cases we must resort to meningeal biopsy. Corticosteroid therapy is usually effective and it is the first line treatment.

Abstract 4977: Chronic mastitis in North Africa: Geographic overlap and a potential precursor comorbidity of inflammatory breast cancer

Abstract North African countries, such as Egypt and Morocco, have a high prevalence of non-infectious, chronic mastitis (up to 10% of patients presenting with breast problems) compared to less than 1% worldwide. This same geographic region also suffers from an unusually high prevalence of inflammatory breast cancer (IBC) - 10-15% of breast cancer cases - versus just 1-2% of cases in the U.S. IBC is a serious public health issue as it is the most lethal form of breast cancer because of the propensity for rapid onset of disseminated metastases, which are present in one-third of cases at diagnosis. It is our hypothesis that this geographic overlap is not coincidental, but that the high level of background chronic breast inflammation changes the mammary microenvironment making it more auspicious for the development of IBC. Here we report our work aimed at determining molecular and histologic criteria to classify mastitis into pathogenic groups in order to rationally guide treatment for this serious inflammatory illness, as well as study its possible role in the development of IBC. We identified 44 cases of chronic mastitis of unknown etiology. Cases were defined as any female patient with histopathological diagnosis of chronic mastitis seen at the 5 study hospitals in Egypt and Morocco from 2008-2011. Exclusion criterion was previous diagnosis of malignancy. Biopsy slides were analyzed by a pathologist and stained for IgG4 and IgG. Out of the 44 cases of chronic mastitis using consensus guidelines and our molecular IgG4 profiling, we identified 10 as idiopathic granulomatous mastitis (IGM) and 17 as breast manifestations of IgG4-related disease. IGM is a rare non-neoplastic, chronic, often severe inflammatory lesion of the breast that mimics carcinoma clinically and radiologically. Treatment strategies include watchful waiting, immunosuppressive therapy, wide local or other excisions, or combinations of the above. IgG4-related disease is a newly recognized fibro-inflammatory condition. It is characterized by the formation of tumefactive lesions, a dense lymphoplasmacytic infiltrate with many IgG4-positive plasma cells, storiform fibrosis, obliterative phlebitis and, frequently, elevated serum IgG4 concentrations. While no randomized clinical trials have been conducted, glucocorticoid treatment is the standard first line therapy and appears to be quite effective in the majority of patients. This series is the largest reported and is the first step toward changing the chronic breast inflammatory landscape in North Africa by classifying the chronic mastitis into pathogenic groups that can guide personalized treatment protocols. Further studies are needed to discern whether effective and timely treatment of these chronic inflammatory conditions may lower the incidence of IBC. Citation Format: Steven G. Allen, Hanna Oltean, Kathy Toy, Omar S. Omar, Tamer Youssef, Mehdi Karkouri, Azza Abdel-Aziz, Ahmad Hablas, Ali Tahri, Celina Kleer, Amr Soliman, Sofia D. Merajver. Chronic mastitis in North Africa: Geographic overlap and a potential precursor comorbidity of inflammatory breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4977. doi:10.1158/1538-7445.AM2014-4977

IgG4-associated cholangitis: a comprehensive review.

IgG4-associated cholangitis (IAC) is a major manifestation of immunoglobulin G4-related disease (IgG4-RD), an inflammatory multiorgan disorder of unknown cause. IAC and autoimmune pancreatitis (AIP) may mimic sclerosing cholangitis, cholangiocarcinoma, or pancreatic carcinoma. Typically, elderly male patients present with abdominal discomfort, weight loss, jaundice, and itch. At present, no accurate diagnostic test for IAC and IgG4-RD is at hand, often causing significant diagnostic delay. Serum IgG4 is only diagnostic when markedly raised (>4× ULN). Imaging in IAC discloses mass-forming lesions and/or strictures in the biliary tract. Histology may show tissue infiltration of IgG4-expressing plasma cells. Diagnostic criteria for histologic and imaging findings, serum tests, organ manifestation pattern, and response to immunosuppressive therapy (HISORt) criteria are used for the diagnosis of IgG4-RD. Still, considering the difficulty in diagnosing IAC and AIP, unnecessary hepatic or pancreatic resections for presumed malignancies occur. The good response to corticosteroid therapy in IAC and other manifestations of IgG4-RD suggests an immune-mediated inflammatory disease. Maintenance immunosuppression after induction of remission is needed in the majority of patients to avoid relapse. The pathogenesis of IAC and IgG4-RD remains poorly understood. Unresolved questions include: (i) Does IgG4 have a pro- or anti-inflammatory role in IAC? (ii) Is IAC a B cell- and/or T cell-mediated disease? (iii) Which are the molecular targets attacked by the immune system in IgG4-RD? Here, we review the diagnostic and therapeutic management of the disease and discuss recent pathophysiological findings, which might help to better understand the molecular mechanisms contributing to IAC and other manifestations of IgG4-RD.

Retroperitoneal disorders associated with IgG4-related autoimmune pancreatitis.

IgG4-related autoimmune pancreatitis is frequently accompanied by relevant lesions in the genitourinary tract and retroperitoneal organs, which cause various clinical problems, ranging from non-specific back pain or bladder outlet obstruction to renal failure. The diagnosis of IgG4-related retroperitoneal fibrosis requires a multidisciplinary approach, including serological tests, histological examination, imaging analysis, and susceptibility to steroid therapy. Radiological examinations are helpful to diagnose this condition, but surgical resection is occasionally unavoidable to exclude malignancy, particularly for patients with isolated retroperitoneal involvement. Steroid therapy is the treatment of choice for this condition, the same as for other manifestations of IgG4-related disease. For patients with severe ureteral obstruction, additional ureteral stenting needs to be considered prior to steroid therapy to preserve the renal function. Some papers have suggested that IgG4-related disease can affect male reproductive organs including the prostate and testis. IgG4-related prostatitis usually causes lower urinary tract symptoms, such as dysuria and pollakisuria. Patients sometimes state that corticosteroids given for IgG4-related disease at other sites relieve their lower urinary tract symptoms, which leads us to suspect prostatic involvement in this condition. Because of the limited number of publications available, further studies are warranted to better characterize IgG4-related disease in male reproductive organs.

Gastric Ulcer: An Old Disease - A New Cause

A 73 year patient presented with melena to our endoscopy unit. He was hemodynamically stable and the haemoglobin was decreased with 113 g/l. The remaining blood tests were normal. Upper endoscopy showed a large bleeding ulcer along the lesser curvature, macroscopically suspicious for malignancy. To control the bleeding and to rule out gastric cancer, the patient was referred to surgery. Two thirds of the stomach, a segment of the transverse colon with mesocolon had to be resected en bloc. Final histology revealed a chronic ventricular ulcer with a distinct lymphofollicular, lymphoplasmacellular and eosinophilic inflammation. The number of IgG4 plasma cells was increased (60 IgG4 positive cells per microscopic visual field, 70-80% IgG4 out of all IgGs). Storiform fibrosis and obliterating phlebitis were found not only within the ulcer base but also extensively in the adjacent soft tissue. Summarizing, our patient suffered from a rare form of a chronic gastric ulceration as a manifestation of IgG4-related disease. IgG4-related disease is an increasingly recognized condition presenting with specific pathological, serologic and clinical features. Its hallmark is the typical histopathological finding as in our case. Type 1 autoimmune pancreatitis and salivary gland disease are the two typical presentations, but IgG4-disease can affect each organ. Because of no further organ involvement, consecutive immunosuppressant treatment was not required. Seven months later gastroscopy showed no signs of recurrence. A gastric ulcer can be the first presentation of IgG4 related disease which needs to be considered as a differential diagnosis in refractory gastritis and cancer suspicious lesions.

Ulcerative Colitis and Immunoglobulin G4

Background/AimsUlcerative colitis (UC) is sometimes associated with autoimmune pancreatitis (AIP). Infiltration of immunoglobulin G4 (IgG4)-positive plasma cells is sometimes detected in the colonic mucosa of AIP or UC patients. This study aimed to clarify the relation between UC and IgG4.MethodsAssociations with UC were reviewed in 85 AIP patients. IgG4 immunostaining was performed on biopsy specimens from the colonic mucosa of 14 AIP and 32 UC patients.ResultsUC was confirmed in two cases (type 1 AIP, n=1; suspected type 2 AIP, n=1). Abundant infiltration of IgG4-positive plasma cells in the colonic mucosa was detected in the case of suspected type 2 AIP with UC and two cases of type 1 AIP without colitis. Abundant infiltration of IgG4-positive plasma cells was detected in 10 UC cases (IgG4-present, 31%). Although 72% of IgG4-absent UC patients showed mild disease activity, 70% of IgG4-present patients showed moderate to severe disease activity (p<0.05).ConclusionsUC is sometimes associated with AIP, but it seems that UC is not a manifestation of IgG4-related disease. Infiltration of IgG4-positive plasma cells is sometimes detectable in the colonic mucosa of UC patients and is associated with disease activity.

Cerebrospinal Fluid Analysis in Immunoglobulin G4-related Hypertrophic Pachymeningitis

To the Editor: Immunoglobulin G4-related disease (IgG4-RD) is characterized by fibrous swelling of affected organs, elevations in serum IgG4 concentrations, and responsiveness to glucocorticoid treatment1. Affected tissues display similar histological features: diffuse lymphoplasmacytic infiltration by numerous IgG4-positive plasma cells, occasional eosinophils, storiform fibrosis, and obliterative phlebitis2. IgG4-related hypertrophic pachymeningitis (IgG4-HP) has been identified as a characteristic central nervous system (CNS) manifestation of IgG4-RD, but comprehensive cerebrospinal fluid (CSF) analyses are substantially lacking3,4. Recently, we demonstrated an intrathecal IgG and IgG4 synthesis in the CSF of a patient with IgG4-HP and suggested IgG4 Indices as safe potential diagnostic tools for IgG4-HP5. Here, we describe 2 new cases of IgG4-HP with CSF evaluation at diagnosis and in response to treatment. In case 1, March 2007, a 56-year-old man was admitted with a 1-year history of right frontal headache. Magnetic resonance imaging (MRI) showed right frontal pachymeningitis. Granulomatous meningeal inflammation was suspected and oral prednisone (1 mg/kg body weight/day) was started with clinical and radiological improvement. Prednisone was discontinued after 8 months, but in July 2008 the headache recurred. Blood and CSF analyses are shown in Table 1. MRI evidenced a right frontotemporal progression of the pachymeningitis (Figure 1A). A meningeal biopsy … Address correspondence to Dr. E. Della-Torre, Department of Medicine and Clinical Immunology, San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy. E-mail: dellatorre.emanuel{at}hsr.it

Raised Numbers of IgG4-Positive Plasma Cells Are a Common Histopathological Finding in Orbital Xanthogranulomatous Disease

ABSTRACTPurpose: To determine the relation of orbital xanthogranuloma with IgG4-related disease.Methods: Retrospective consecutive case series over a period of 25 years. We searched our charts for histologically confirmed orbital xanthogranuloma. Patient files were reviewed for clinical and follow up data including presence or absence of systemic non-ophthalmic manifestations of IgG4 related disease. Slides were re-examined and histopathological classification was re-assessed. Sixteen cases of orbital xanthogranuloma were evaluated. Immunohistochemical stains for IgG and IgG4 were performed. Positive immunohistochemical staining required increased IgG4-positive plasma cells in the involved tissues scored as >50 per high-power field, with IgG4/IgG ratio >0.40.Results: According to the criteria described above 8/16 (50%) cases showed increased numbers of IgG4-positive plasma cells in the specimens. Two of these patients may have had signs of systemic diseaseConclusion: Raised numbers of IgG4-positive plasma cells are a common finding in histopathological specimens of xanthogranulomatous disease of the orbit and are often not indicative for IgG4 related systemic disease.

Cutaneous plasmacytosis as a skin manifestation of IgG4-related disease

Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a fibro-inflammatory condition that has distinctive clinical features involving multiple organs, such as the pancreas, salivary and lacrymal glands (Mikulicz's disease), biliary tract, peritoneum, pituitary gland, lung, kidney and aorta [1, 2]. Mass-forming, sclerosing lesions are commonly seen in affected organs and systemic corticosteroids are effective for these conditions. Histopathologically, dense lymphoplasmacytic infiltration, storiform [...]