Role of Immunohistochemistry and serology in subclassifying the Inflammatory Bowel Disease cases diagnosed as Inflammatory Bowel Diseases-unclassified on colonic biopsies

Background: Inflammatory bowel diseases (IBDs) mainly consist of Crohn's Disease (CD) and Ulcerative Colitis (UC). These two categories have overlapping histopathological features and sometimes it is difficult to diagnose them into distinct category and such biopsies are categorised as Inflammatory Bowel Disease (IBD-U). Recently, there has been an increase in interest to discover new biomarkers of IBD to differentiate UC and CD and predict their prognosis. Method: In the present study, 273 non-neoplastic colonic biopsies with clinicoendoscopic features of IBD were studied and categorized into UC (88; 32.3%) and CD (03; 1.1%) but a major chunk remained in category of IBD-U (182; 66.6%). 161 (58.9%) of these biopsies were then subjected to IHC for RB protein and ?-catenin and Serology for pANCA and ASCA was done in only 85 (31.13%) of these selected cases for identification of UC and CD on colonic biopsies. Result: 161 biopsies that were subjected to IHC analysis included 57 cases of UC, 03 cases of CD, and rest 101 cases of IBD-U. Out of 101 cases of IBD-U, 87 (86.13%) cases were reclassified as UC (61; 60.3%) and CD (14; 13.86%) on the basis of results of IHC and Serology. Conclusion: The two major tools IHC for ?-catenin and RB protein and the assay of serum ASCA and p-ANCA along with proper history and clinical presentation can act as a good adjunct to conventional H and E in subclassifying cases of IBD-U into UC and CD.

Perinuclear anti neutrophil cytoplasmic antibody vasculitis with nonspecific muscle pain

This is a case report describing p-ANCA vasculitis presenting with nonspecific muscle pain. It is a very uncommon finding seen in p-ANCA vasculitis patients which they usually present with palpable purpura alone. In this case, along with nonspecific muscle pain, renal involvement of the disease has been explained and there are no upper and lower respiratory tract complaints which favours more towards microscopic polyangitis.

Vasculitis asociada a anticuerpos anticitoplasma de neutrófilos: poliangeítis microscópica / Antineutrophil Cytoplasmic Antibody Associated Vasculitis: Microscopic Polyangiitis

La poliangeítis microscópica se define como una enfermedad autoinmune, multisistémica, de rara incidencia, asociada a anticuerpos anticitoplasma de neutrófilos. Se caracteriza por presentar vasculitis necrotizante de pequeños vasos, no granulomatosa y ausencia de depósito de inmunocomplejos, que afecta predominantemente el tejido renal, pulmonar y cutáneo. Se presenta un paciente masculino, 49 años, sin antecedentes patológicos. Presenta cuadro clínico de 30 días de evolución con tos seca de tipo irritativa, que evoluciona a tos productiva, hemoptisis, disnea de moderado esfuerzo, astenia y edema con fóvea en zonas en declive. Tenía anemia grave y los estudios imagenológicos de tórax evidenciaron infiltrados difusos con aspecto de vidrio deslustrado. Se inició terapia inmunosupresora con metilprednisolona y ciclofosfamida y profilaxis antibiótica. Se obtuvo una disminución en el puntaje de la escala de actividad vasculítica y la posterior remisión; sin embargo, debido al daño tisular renal, no hubo mejoría en la tasa de filtrado glomerular, por lo que el paciente se mantiene en terapia de sustitución renal permanente. Es trascendental el conocimiento de las manifestaciones clínicas, procedimiento diagnóstico y tratamiento de esta enfermedad, ya que, a pesar de su rara incidencia, posee una llamativa morbimortalidad que puede modificarse significativamente con un diagnóstico y tratamiento oportunos(AU)

Microscopic Polyangiitis is defined as an autoimmune, multisystemic, low prevalence disease, associated to antineutrophil cytoplasmic antibody. Characterized by necrotizing vasculitis of small vessels, with no granulomatous inflammation and absence of immune complex deposits, predominantly affecting renal, pulmonary and cutaneous tissue. 49-year old male patient with no past medical history. Refers symptomatology that started thirty days ago, characterized by dry cough, that evolves to productive cough, hemoptysis, exertional dyspnea, asthenia and pitting edema. Laboratory tests show severe anemia, glomerular filtration rate of 6.9 ml/min/1.73m2, hematuria, proteinuria, positive presence of antineutrophil cytoplasmic antibodies and anti-myeloperoxidase antibodies, additional thoracic imaging shows ground glass opacities consolidations. Immunosuppressive therapy is started with Methylprednisolone and Cyclophosphamide along with antibiotic prophylaxis, resulting in a decrease in the vasculitis activity score with subsequent remission; however due to renal tissue damage, there is no improvement in the glomerular filtration rate and the patient continues receiving renal replacement therapy. Due to its striking morbidity and mortality, we consider of great importance the knowledge of its clinical presentation, diagnostic procedures and treatment, in order to obtain a positive impact on the patient's quality of life and survival rate(AU)

A Case of Microscopic Polyangiitis Initially Suspected with Henoch-Schonlein Purpura Nephritis

Microscopic polyangiitis (MPA) is systemic small vessel vasculitis that is very rare in childhood. MPA is characterized by pauci-immune necrotizing small vessel vasculitis without clinical or pathological evidence of necrotizing granulomatous inflammation. Approximately 90% of patients have glomerulonephritis that is accompanied by a variety of other organ involvement. A 10-year-old girl visited our clinic with clinical manifestations suggestive Henoch-Schonlein purpura nephritis such as purpuric skin rash, abdominal pain, arthralgia on both knees, massive proteinuria and microscopic hematuria. So initially we suspected Henoch-Schonlein purpura nephritis. However, later her perinuclear-antineutrophil cytoplasmic antibodies(p-ANCA) test was positive, and her renal biopsy was consistent with microscopic polyangiitis. We began steroid therapy, combined with cyclophosphamide, ACE inhibitor. Currently she is a 12-year old, and until now she has been regularly examined in the outpatient. We report a case of microscopic polyangiitis initially suspected with Henoch-Schonlein purpura nephritis.

Reversible Sensorineural Hearing Loss due to Pachymeningitis Associated with Elevated Serum MPO-ANCA

Hypertrophic pachymeningitis is a progressive disease resulting in a diffuse thickening of dura mater due to inflammation, tumor or autoimmune diseases, but most cases are idiopathic. It is seldom reported to be related to sensorineural hearing loss, but it can cause sensorineural hearing loss which can be potentially reversed through treatment. Here, we report the case of a 54-year-old woman who had progressive, bilateral, worse in the left, sensorineural hearing loss and visual disturbance with an accompanying headache over several months. Brain MRI showed diffusely thickened dura mater, highly enhanced after gadolinium administration, which was consistent with pachymeningitis. It was assumed to be related to autoimmune pathogenesis on the basis of elevated serum myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) titers. After empirical steroid and cyclophosphamide therapy, auditory impairment improved, especially in the high frequency region of the pure tone audiogram, and significant improvement in the word recognition test. Moreover, a follow-up MRI revealed much decreased enhancement of the dura mater, and the MPO-ANCA titer decreased to within the normal range. In the case of rapidly progressive sensorineural hearing loss or hearing impairment accompanying other cranial neuropathy, pachymeningitis should be taken into consideration, and brain MRI with gadolinium enhancement is the best method of detecting it. Also, to ensure proper treatment, a cautious evaluation including an ANCA work-up should be performed.

A Case of p-ANCA-Positive Propylthiouracil-Induced Pyoderma Gangrenosum

Propylthiouracil is a common medication used in patients with hyperthyroidism; it can cause perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) in some patients with Graves' disease. This antibody has been associated with various forms of vasculitis and neutrophilic dermatosis. Herein, we report a patient who presented with cutaneous manifestations of pyoderma gangrenosum with simultaneous development of p-ANCAs during PTU therapy for Graves' disease.

Immunofluorescence (IF) Pattern, Autoantigens of Anti-neutrophil Cytoplasmic Antibodies (ANCA) and Their Clinical Associations / Jurnal Sains Kesihatan Malaysia

Antineutrophil cytoplasmic antibodies (ANCA) are autoantibodies directed against primary granules of neutrophils and monocytes’ lysosomes. In general, c-ANCA is strongly associated with vasculitic disorders mainly in ANCA-associated systemic vasculitis (AASV). p-ANCA have been identified in several diseases such as primary (AASV) and secondary vasculitis such as collagen vascular diseases, rheumatoid arthritis and inflammatory bowel diseases given the term ‘ANCA-associated disease.’ The objective of this study was to determine the rate of ANCA positivity by indirect immunofluorescent (IF) and enzyme linked immunosorbent assay (ELISA) and its association with AASV and ANCA associated diseases. Serum from patients with history suspicion of systemic vasculitis were tested for ANCA by IF. Those samples positive for ANCA by IF were further tested for antibodies against myeloperoxidase (MPO) and proteinase 3 (PR3) using the ELISA. Clinical data from medical records were obtained and analyzed. Of 468 samples, a total of 110 were positive for ANCA by IF. IF results showed a p-ANCA pattern in 96 patients and c-ANCA in 14. Of 110 IF positive ANCA, 45 patients were positive by ELISA. Seventeen were positive for MPO-ANCA, 9 were PR3-ANCA positive and 19 were both MPO and PR3 positive. Only 2 patients were classified AASV ie Wegener granulomatosis and the other with microscopic polyangiitis. The remaining patients (n = 108) may be classified as ANCA associated diseases. Our study showed that p-ANCA (87.3%) was the more common ANCA pattern and 40.9% of IF positive samples were positive for PR3- and MPOANCA.

Anticorpos contra o citoplasma de neutrófilos / Antineutrophil cytoplasmic antibodies

Os auto-anticorpos antiantígenos citoplasmáticos de neutrófilos (ANCA) têm importante associação ao diagnóstico e possível monitoramento de uma significante parcela de doenças auto-imunes. A Proteinase 3 é o principal antígeno presente no tipo demarcação citoplasmática granular difusa (c-ANCA), e a Mieloperoxidase na marcação perinuclear (p-ANCA) em ensaios de imunofluorescência indireta (IFI) em neutrófilos fixados em etanol. A vasculite sistêmica compreende uma série de síndromes caracterizadas por dividir uma base histopatológica comum: inflamação nos vasos sangüíneos resultando em obstrução vascular com subseqüente isquemia e enfartamento tissular. A vasculite constitui um grupo heterogêneo de doenças que possuem como característica comum à inflamação destrutiva da parede de vasos sangüíneos. O papel potencializador de ANCA sobre as lesões é descrito em estágios iniciais de vasculite sistêmica pelo fato deste promover o recrutamento e adesões entre neutrófilos e células endoteliais.O presente trabalho teve como objetivo enfocar o papel do c-ANCA e p-ANCA no diagnóstico laboratorial de Vasculite Sistêmica e o levantamento de exames efetuados no período de 16/04/04 a 20/04/06 para estes mesmos marcadores no laboratório de ImunologiaClínica do Hospital Universitário Polydoro Ernani de São Thiago. Neste levantamento pudemos constatar uma reduzida parcela de resultados positivos para c-ANCA (15%) e p-ANCA (39%), fato este devido à larga gama de doenças com sintomatologias semelhantes às doenças relacionadas à ANCA, possuindo, porém ANCA negativo.A avaliação clínica é importante no manejo de doenças auto-imunes, mas o laboratório representa papel decisivo na avaliação dessas doenças. Testes laboratoriais auxiliam ao estabelecer o diagnóstico, na monitorização do curso da doença, na predição de sua evolução,na decisão acerca da terapêutica, na avaliação da resposta à terapia e também para o estudo da etiologia ou patogênese das doenças auto-imunes

A Case of Recurrent Pulmonary Hemorrhage in p-ANCA-Related Vasculitis Patients on Hemodialyis / 대한신장학회지

ANCA-associated vasculitis is one of the immunologic cause of diffuse alveolar hemorrhage (DAH). We experienced a rare case of recurrent DAH in a 67-year-old man with ANCA-associated vasculitis who had been on maintenance hemodialysis. Two years ago, he presented with renal failure and hemoptysis. Hemoptysis caused by DAH was resolved immediately and hemodialysis was applied because of persistent uremic symptom. On maintenance hemodialysis, three recurrences have happened so far. At present, oral prednisolone and oral cyclophosphamide are being maintained during outpatient follow-up. Our report suggests that the nephrologist must be concerned about the possibility of recurrent aleveolar hemorrhage in ANCA associated renal disease patients and consider immunosuppressive treatment, even though the patient has been on maintenance hemodialysis.

A Case of Microscopic Polyangiitis with Acral Necrosis as Skin Manifestation / 대한피부과학회지

Microscopic polyangiitis (MPA) is a systemic vasculitis that is histologically characterized by small vessel involvement. Although MPA is primarily associated with necrotizing and crescentric glomerulonephritis and pulmonary capillaritis, MPA often has cutaneous features. We report a case of microscopic polyangiitis with acral necrosis as the skin manifestation. A 56-year-old man presented with acral dry gangrene on tip of finger and toe and reticulated erythema on leg. He had suffered from proteinuria, hemoptysis, and arthralgia. Histopathologically, small vessel vasculitis without granuloma was seen. A high serum level of pANCA was detected by ELISA. This is a relatively rare disease, which has a poor prognosis in the absence of aggressive therapy, and is infrequently reported in dermatologic journals in Korea.

Propylthiouracil-associated p-ANCA Positive Vasculitis with Focal Segmental Glomerulosclerosis / 대한신장학회잡지

Antineutrophilic cytoplasmic antibody (ANCA) associated vasculitis has been reported in Graves' disease patients treated with propylthiouracil (PTU). In most cases, it's renal involvements has been known as crescentic glomerulonephritis. A 41-year-old female patient with hyperthyroidism has been treated with PTU for 3 years. The patient had developed isolated hematuria and polyarthralgia with p-ANCA positivity, 6 months and 10 months after PTU treatment, respectively. She had been continuously treated with PTU until she was admitted at our hospital. Three months before admission, polyarthralgia was aggravated and purpura in both lower legs and hands was developed. Urinalysis revealed hematuria, proteinuria. Serologic evaluation showed p-ANCA positive. Skin biopy showed leukocytoclastic vasculitis and renal biopsy showed focal segmental glomerulosclerosis (FSGS). She was diagnosed as PTU-associated vasculitis with FSGS. Polyarthralgia and purpura were improved after discontinuing the PTU with prednisolone treatment but hematuria, proteinuria were not changed. We suggest that progression of PTU-associated focal segmental necrotizing glomerulonephritis to FSGS over two years might be due to continued PTU medication.

A Case of Death Due to Spontaneous Intraperitoneal Bleeding in P-ANCA Positive Small Vessel Vasculitis / 대한신장학회잡지

P-ANCA small vessel vasculitis is multisystemic disease, especially frequently involving the kidney. Diagnosis is delayed because it's non-specific clinical manifestation. Recently ANCA becomes available tools for diagnosis of vasculitis. Infection and gastrointestinal complications are relatively common in vasculitis. But spontaneous rupture of gastrointestinal artery is a rare complication. A 61-year-old housewife was admitted due to poor oral intake, weight loss and microscopic hematuria. Renal biopsy showed an extensive necrotizing glomerulonephritis, consistent with Wegener's granulomatosis or microscopic polyangitis. Serum test showed positive for P-ANCA. Despite steroid therapy, she expired due to spontaneous rupture of right gastroepiploic artery.

One Case of Microscopic Polyangiitis / 대한내과학회지

Microscopic polyangiitis is a primary systemic vasculitis which involve small arterioles and capillaries. Clinical manifestations show generalized weakness, fever, myalgia, weight loss. oliguria, proteinuria, skin rash, neuromuscular symtoms, and pulmonary, gastrointestinal symtoms. Prednisolone and cyclophosphamide therapy is effectve, more than 80% of patients with microscopic polyangiitis survive for longer than 5years. However, about 50% of patients will have at least one relapse in the 4-5years after initial treatment. There is a very strong correlation between the presence of ANCA(especially p-type) and microscopic polyangiitis. We herein report a case of microscopic polyandiitis with the review of literature. A 65 years-old woman admitted to our hospital due to general weakness, fever, generalized edema, and dyspnea. Laboratory result showed high serum creatinine and CRP, moderate proteinuria, and microscopic hematuria. P-ANCA was 1:1280 positive in indirect immunofluorescence method, and kidney biopsy showed focal segmental necrotizing glomerulonephritis, crescent formation, fibrin clots, PMN and lymphocytes infiltrations in small arterioles and capillries. Immunofluorescence study was negative. Her clinical feature, laboratory findings, and the kidney biopsy result were compatible with microscopic polyangiitis. The patient had been treated with prednisolone and cyclophosphamide. P-ANCA titration was decreased 1:320 at the 19th day of treatment and was negative about 2months later.