Crohn''s Disease Associated with Cyclic Neutropenia

Crohn's disease and neutropenia unrelated to drug therapy is a rare association. We present a case of Crohn's disease associated with cyclic neutropenia. Our patient, observed over 10 yr, is unique due to the lack of recurrent bacterial infections or other associated sequelae of the neutropenic state. There was no consistent association between white blood cell cycling and exacerbations of her Crohn's disease. However, the latter did appear to worsen the neutropenic state. A clear pattern of cyclic neutropenia became apparent only when the disease was quiescent and all medications had been discontinued. We report this case for its value in pursuing clinically and therapeutically appropriate options, including surgery and drugs with neutropenic potential, in patients with Crohn's disease and, possibly, white blood cell abnormalities.     

Intramedullary neutrophil phagocytosis by histiocytes in autoimmune neutropenia of infancy

We describe a case of autoimmune neutropenia of infancy in which active phagocytosis of mature myeloid cells by bone marrow histiocytes was observed. This finding in the routine hematological investigation has not been reported so far and might be helpful in suggesting the diagnosis of autoimmune neutropenia of infancy, and also in understanding the pathogenesis of peripheral neutropenia in this disease.     

Sjogren's syndrome in association with Crohn's disease

SUMMARY: Crohn's disease has many autoimmune extraintestinal manifestations, such as arthritis, polymyositis, and erythema nodosum. However, an association between Crohn's disease and Sjogren's syndrome, an autoimmune disease, has rarely been reported. We describe the fourth case of Sjogren's syndrome in association with Crohn's disease. The patient is a 43-year-old African-American female diagnosed with Crohn's disease in 1981. Twenty years later, she developed abdominal pain, arthralgias, and sicca symptoms. Further evaluation led to a diagnosis of Sjogren's syndrome. Sjogren's syndrome should be considered in patients with underlying Crohn's disease who develop a constellation of constitutional, joint, and sicca symptoms.     

Autoimmune thyroid disease (Graves' disease and hashimoto's thyroiditis) in two patients with Crohn's disease: case reports and literature review

An increased prevalence of the association between autoimmune thyroid diseases and ulcerative colitis has been suggested, however, not with Crohn's disease, as only 7 cases of thyroid disease coexisting with Crohn's disease have been reported. Herein, we describe 2 patients with Crohn's disease complicated with Graves' disease or autoimmune thyroiditis, and also review other cases with those complications. Some immunological processes are suggested to be implicated in the pathogenesis of this association, however, the exact mechanism remains unclear.     

Fulminant Crohn's colitis after allogeneic stem cell transplantation

We report a case of fulminant Crohn's colitis that occurred following non-myeloablative allogeneic stem cell transplantation for Hodgkin's lymphoma. Adoptive transfer of inflammatory bowel disease by haematopoietic cells is recognised in several animal models of inflammatory bowel disease and remission of Crohn's disease has been reported in patients who have received a bone marrow transplant. However, adoptive transfer of Crohn's disease susceptibility leading to phenotypic manifestation of the disease after transplantation has not been previously reported. Having ruled out an infective cause of a colitis in this case, we speculated that adoptive transfer of Crohn's disease may have occurred and performed a genetic analysis of known susceptibility loci for significant donor-recipient mismatches. The donor and recipient had several haplotype mismatches in HLA class III genes at the IBD3 locus. In addition, the donor (but not the recipient) had a polymorphism of the 5' UTR of NOD2/CARD15 that may be associated with Crohn's disease. This case highlights the question of whether adoptive transfer of Crohn's disease can occur between allogeneic stem cell transplant donor and recipient, in a similar fashion to that reported for other autoimmune diseases. This report should also stimulate debate regarding the need for stem cell transplant donor screening for inflammatory bowel disease.     

Healing of severe perineal and cutaneous Crohn's disease with hyperbaric oxygen

Recurrent perineal Crohn's disease can be an extremely debilitating complication that may be difficult to treat. We report a patient with progressively worsening perineal and biopsy-proven cutaneous Crohn's disease that had been refractory to surgery and medical treatment (sulfasalazine, steroids, 6-mercaptopurine, metronidazole, antibiotics). As the lesions were reminiscent of problem wounds occurring in other situations, hyperbaric oxygen treatment was instituted while the patient was continued on metronidazole. Response was dramatic with almost immediate relief of symptoms and regression within 2.5 mo of wounds that had previously defied therapy for 8 yr. Clinical remission has not been sustained as four subsequent courses of hyperbaric oxygen have been given over a period of 11 mo. However, the patient has been essentially asymptomatic since her initial course and the extent of her cutaneous disease has been minimal compared with that before hyperbaric oxygen. Hyperbaric oxygen treatment is costly and should not be routinely used in every patient with perineal Crohn's disease. However, this case report may herald an advance in the understanding of the pathogenesis of this complication and ultimately, its therapy.     

Sigmoid volvulus as a complication of ileal Crohn's disease

Intestinal volvulus in patients with Crohn's disease is rare and we could find only one report of sigmoid volvulus with active Crohn's colitis. We have seen a 54-year-old woman with long-standing Crohn's disease who developed large-bowel obstruction. After eventual detorsion of the sigmoid volvulus, we found that her ileum was involved with active Crohn's disease and that her colonic mucosa was free of mucosal lesions. In this case, we suspect that the reactivation of the ileal Crohn's disease as well as other features commonly associated with Crohn's disease contributed to the development of sigmoid volvulus by causing fixation, torsion, and dilatation of distal bowel.     

Coombs-positive autoimmune hemolytic anemia in Crohn's disease

BACKGROUND: Anemia often occurs in patients with inflammatory bowel diseases. However, hemolytic anemia is a rare complication and is associated with Coombs-positive autoimmune disorders. There are several reports of autoimmune hemolytic anemia in patients with ulcerative colitis, whereas there are only four reports of this complication in patients with Crohn's disease. We report a case of a severe course Coombs-positive hemolytic anemia in a patient with Crohn's disease, which was refractory to medical treatment but resolved after subtotal colectomy. CASE REPORT: A 29-year-old patient was submitted to our clinic several times because of a severe course of inflammatory bowel disease and additionally a Coombs-positive autoimmune hemolytic anemia. Histology indicated severe Crohn's disease, but neither medical treatment with steroids, nor with methotrexate, cyclosporine or tumor necrosis factor-alpha antibody had been successful in resolving the intestinal inflammation and the hemolytic anemia. As colonoscopy revealed a pancolitis and dysplastic changes, even in the less inflamed areas of the colonic mucosa, subtotal colectomy was indicated. Half a year later we observed clinical and immunological signs of complete remission (no gastrointestinal symptoms, negative Coombs test). CONCLUSION: Autoimmune hemolytic anemia is a rare complication of inflammatory bowel disease and has been almost exclusively described in ulcerative colitis. The etiology is not yet completely understood. Presumably, the colon displays a role in the production of anti-erythrocyte antibodies. The therapy of choice in Crohn's associated hemolytic anemia is thought to be medical treatment with corticoid steroids. Some authors additionally prefer immunmodulators. However, in the case presented, colectomy (without splenectomy) was necessary to resolve refractory hemolysis and the severe course of Crohn's disease.     

Overlap syndrome between autoimmune hepatitis and primary sclerosing cholangitis in two cases

The overlap syndrome between autoimmune hepatitis and primary sclerosing cholangitis is a rare condition and only few cases have been published, partly associated with ulcerative colitis, but not with Crohn's disease. We report an autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome in a female patient with Crohn's disease. In addition, a second case of overlap syndrome is reported in a man without inflammatory bowel disease. A 24-year-old woman was referred with a 10-month history of diarrhoea and biochemical changes including elevated serum levels of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and immunoglobulin G. Enzyme linked immunosorbent assay showed that antinuclear autoantibodies were elevated. Immunofluorescence for perinuclear-staining antineutrophil cytoplasmatic antibodies was positive. Diagnostic criteria of definite autoimmune hepatitis according to the International Autoimmune Hepatitis Group were fulfilled. Liver biopsy simultaneously showed criteria of autoimmune hepatitis and primary sclerosing cholangitis. Endoscopic retrograde cholangiography demonstrated features of primary sclerosing cholangitis. Colonoscopy and colonoscopic biopsies indicated an active Crohn's disease affecting the terminal ileum and the ascending and transverse colon. Furthermore, we report the case of a 28-year-old man with known primary sclerosing cholangitis for the previous 6 years, and who developed jaundice and a marked increase of aspartate aminotransferase, alanine aminotransferase and immunoglobulin G, leading to the diagnosis of definite autoimmune hepatitis. A review of the literature revealed only 16 cases of an autoimmune hepatitis/primary sclerosing cholangitis syndrome in patients without inflammatory bowel disease or in association with ulcerative colitis. We report two additional cases, one case showing an association with Crohn's disease.     

Elevated Serum Vascular Endothelial Growth Factor in Children and Young Adults with Crohn's Disease

Vascular endothelial growth factor (VEGF) is acytokine released by fibroblasts, epithelial cells, andleukocytes that potentiates vascular permeability andgrowth of new capillaries. Because of these multiple effects, VEGF has been postulated to play arole in the pathogenesis of autoimmune disease, as wellas in wound healing. We hypothesized that VEGF waspotentially important in mediating the vascularpermeability and angiogenesis seen in Crohn's disease, andtherefore that VEGF would be increased in the serum ofchildren with Crohn's disease. Serum was obtained from73 children and young adults with Crohn's disease, 47 with ulcerative colitis, and 29 controls.VEGF levels were measured by enzyme-linked immunosorbentassay. Mean VEGF levels were significantly higher inpatients with Crohn's disease (436.4 ± 37.2pg/ml) than in ulcerative colitis (306 ± 41.1pg/ml) or control (167.8 ± 29.6 pg/ml) patients.Serum VEGF also correlated significantly with diseaseactivity, being elevated in patients withmoderate/severe Crohn's disease and ulcerative colitis. Weconclude that serum VEGF is released by inflamed tissuesin children with Crohn's disease. This multifunctionalcytokine could promote inflammation by increasing vascular permeability or promote wound healingby mediating capillary growth.     

Acute paraplegia after the initiation of anti-tumour necrosis factor-alpha therapy for Crohn's disease

Therapies aimed at inhibiting tumour necrosis factor are currently successfully administered to an increasing number of patients with autoimmune diseases. Infliximab has been approved to induce and maintain remission in Crohn's disease and fistulizing Crohn's disease. We report a case of acute-onset flaccid paraplegia after the initiation of anti-tumour necrosis factor therapy (infliximab) for Crohn's disease. Neuroimaging findings revealed an extensive longitudinal myelopathy. Two months later, no abnormal signal intensity was observed in the spinal cord and after 4 months, the patient presented improvement of motor function. A possible correlation between anti-tumour necrosis factor therapy and acute myelitis is discussed. This case highlights that patients developing new neurological symptoms while on anti-tumour necrosis factor medication should be monitored closely.     

Association of the lymphoid tyrosine phosphatase R620W variant with rheumatoid arthritis, but not Crohn's disease, in Canadian populations

OBJECTIVE: A single-nucleotide polymorphism in the PTPN22 gene encoding the lymphoid protein tyrosine phosphatase (Lyp) has recently been identified as a functional variant associated with susceptibility to rheumatoid arthritis (RA), type 1 diabetes, and systemic lupus erythematosus. To determine whether association of this variant (PTPN22 1858T) with RA is reproducible and is also observed in another autoimmune condition, Crohn's disease, we investigated the association between the PTPN22 1858T allele and RA and Crohn's disease in a Canadian population. METHODS: Two RA case-control cohorts representing a total of 1,234 patients and 791 healthy controls as well as a cohort of 455 patients with Crohn's disease and 190 controls were genotyped for the PTPN22 C1858T polymorphism, and genotype frequencies were compared between patients and controls. RESULTS: Significant association of the PTPN22 1858T allele with RA was detected in both the Toronto-based RA cohort (P = 1.6 x 10(-6), odds ratio [OR] 1.8) and the Halifax-based RA cohort (P = 9.4 x 10(-4), OR 1.94). Association of the risk allele with RA was not affected by sex, age at disease onset, or the presence of either rheumatoid factor or rheumatoid nodules. No association between the PTPN22 risk allele and Crohn's disease was detected. CONCLUSION: These observations confirm the association of RA susceptibility with the PTPN22 1858T allele. However, the data also reveal a lack of association between this variant and Crohn's disease, suggesting that the PTPN22 1858T allele is a risk allele for multiple, but not all, autoimmune diseases.     

Autoimmune neutropenia [see comments]

There have been several new developments in the field of autoimmune neutropenia over the past decade. Neutropenia caused by antibodies directed against granulocyte precursor cells, the oligoclonal nature of antineutrophil antibodies, and the expanding knowledge of neutrophil antigens, particularly in relationship to autoantibodies, are exciting new areas of investigation. Knowledge has also been advanced in the effector mechanisms of neutrophil autoantibodies and the effect of autoantibodies on the neutrophil function. In addition, some clinical syndromes of immune neutropenia have been better defined over the past decade, such as autoimmune neutropenia of infancy and chronic idiopathic neutropenia in adults. The past decade also saw interesting developments in the treatment of immune neutropenia, particularly in the use of gammaglobulin preparations and more recently in the advent of hematopoietic growth factors. This review focuses on these newer aspects of autoimmune neutropenia.     

Familial Crohn's disease with systemic lupus erythematosus

We describe a young Japanese woman who was diagnosed with Crohn's disease affecting the ileum, transverse colon, and rectum, as confirmed by barium studies, colonoscopy, and histopathological examination. Her father and sister also had Crohn's disease. After a 4-yr course of sulfasalazine and elemental diet therapy, she was readmitted for perianal abscess associated with the presence of pancytopenia, microhematuria with granular cast, hypocomplementemia, and high titers of autoimmune antibodies (anti-ANA and anti-dsDNA antibodies). Based on these features, a diagnosis of systemic lupus erythematosus (SLE) was made. Despite the rarity of such combination (Crohn's disease with SLE), patients with Crohn's disease who develop such clinical findings might need evaluation for SLE.     

Myasthenia gravis in a patient affected by glycogen storage disease type Ib: a further manifestation of an increased risk for autoimmune disorders?

Glycogen storage disease type Ib (GSD Ib, OMIM 232220) is an inborn disorder of glucose metabolism, caused by mutations in the G6PT gene, encoding a glucose 6-phosphate transporter (G6PT). GSD Ib is mainly associated with fasting hypoglycaemia and hepatomegaly. Most GSD Ib patients also show neutropenia and neutrophil dysfunction and therefore are at risk of developing severe infections and inflammatory bowel disease (IBD). An increased risk for autoimmune disorders, such as thyroid autoimmunity and Crohn-like disease, has also been demonstrated, but no systematic study on the prevalence of autoimmune disorders in GSD Ib patients has ever been performed. We describe a 25-year-old patient affected by GSD Ib who developed 'seronegative' myasthenia gravis (MG), presenting with bilateral eyelid ptosis, diplopia, dysarthria, severe dysphagia, dyspnoea and fatigue. The repetitive stimulation of peripheral nerves test showed signs of exhaustion of neuromuscular transmission, particularly evident in the cranial area. Even in the absence of identifiable anti-acetylcholine receptor antibodies, seronegative MG is considered an autoimmune disorder and may be related to the disturbed immune function observed in GSD Ib patients.     

Autoimmune neutropenia associated with multiple sclerosis

A 53-year-old Japanese man with multiple sclerosis developed autoimmune neutropenia. The neutrophil count was consistently less than 0.2 x 10(9)/l, irrespective of the disease activity of multiple sclerosis or the administration of immunosuppressive agents or granulocyte colony-stimulating factor. After high-dose gamma-globulin therapy was started, temporary increases in the neutrophil count were observed. Despite a wide spectrum of clinical manifestations in multiple sclerosis, autoimmune neutropenia has never been reported previously.     

Case report: periodical infliximab administration enabled closure of colostomy in fistulating perianal Crohn's disease]

A 29-year old woman with Crohn's disease was performed colostomy due to severe perianal abscess. Her disease had been easy to recur and she was admitted to hospital for intestinal bleeding caused by acute exacerbation in Crohn's disease on October 2006. The bleeding was stopped rapidly and clinical remission was maintained with bimonthly administration of infliximab. Finally, her colostomy was closed after 5 years 8 months. Periodical treatment of infliximab not only prevented recurrence but also enabled closure of colostomy in fistulating perianal Crohn's disease.     

Long-term remission of Crohn's disease treated with thalidomide: A seminal case report

A 31-year-old female with severe Crohn's disease for 15 years who had been treated with corticosteroids and 6-mercaptopurine, was treated with thalidomide initially for erythema nodosum. While on thalidomide all symptoms of Crohn's disease disappeared and she was able to discontinue all other drugs. At this writing she has been on thalidomide as sole therapy for over 4 years with the exception of a 5-week hiatus, during which time her symptoms recurred, but again disappeared after resumption of thalidomide therapy. This case suggests that thalidomide may be a useful therapy for Crohn's disease and provides impetus for a clinical trial of thalidomide for Crohn's disease. This revised version was published online in June 2006 with corrections to the Cover Date.     

Crohn's disease complicated by relapsed extranodal Hodgkin's lymphoma: prolonged complete remission after unmanipulated PBPC autotransplant

Crohn's disease and ulcerative colitis are inflammatory bowel diseases (IBD), which are thought to result from an inappropriate immunologic (autoimmune) response to luminal antibodies. Allogeneic stem cell transplantation (SCT) performed for coincidental diseases is able to cure both leukaemia and Crohn's disease. Autologous SCT is currently performed worldwide for severe autoimmune diseases (SADs) because of its reduced transplant-related mortality (TRM). We report the case of a 30-year-old male patient with a 10-year history of severe Crohn's disease, who developed Hodgkin's disease and received an unmanipulated peripheral blood autologous transplant. Three years after the transplant the patient is in complete treatment-free remission of both diseases.     

Prolonged fever after Infliximab infusion

Pharmacologic management for ulcerative colitis (UC) has recently been expanded to include antitumor necrosis factor (TNF) therapy for severe disease. Infliximab, a chimeric monoclonal antibody directed again TNF α was first tested in patients with Crohn’s disease. In addition to serious infections, malignancy, drug induced lupus and other autoimmune diseases, serum sickness-like reactions, neurological disease, and infusion reactions further complicate the use of Infliximab. We report a case of prolonged fever after Infliximab infusion to treat steroid refractory UC.