Exclusion Of Infectious Causes Research Articles

Inflammatory Bowel Diseases and Kidney Transplantation: A Narrative Review of Clinical Management Approaches.

Inflammatory bowel disease is not uncommon among kidney transplant recipients. In transplant patients with chronic diarrhea and abdominal pain, de novo inflammatory bowel disease can be considered among differential diagnoses, after exclusion of infectious causes and drug-induced diarrhea. Inflammatory bowel disease, in the cnnnontext of organ transplant, is associated with a higherrisk of morbidity, increased rate of hospitalization, and higher mortality.Therefore, a multidisciplinary approach, before and after transplant, among a gastroenterologist specialized in inflammatory bowel disease, a gastrointestinal surgeon, and a transplant clinician is essential, given the higher clinical complexity for this subgroup of patients. Limited data are available on management of inflammatory bowel disease in kidney transplant recipients, although the concurrent use of immunosuppressive therapy can mitigate flare-ups but with increased infection risks. Colorectal cancer can be a serious complication of inflammatory bowel disease; hence, patient compliance with regular colonoscopy surveillance programs is crucial. Patients with inflammatory bowel disease who are undergoing kidney transplant have a shorter overall survival rate compared with matched control groups. However, inferences based on studies involving inflammatory bowel disease in kidney transplant recipients are blighted by small sample sizes,thus making it difficult to draw accurate conclusions. Our review was undertaken to comprehensively report the clinical approaches to kidney transplant recipients with inflammatory bowel disease, describing their clinical course, outcomes, and management plan.

Challenges in the diagnosis of leptomeningeal dissemination of glioblastoma in a patient with fever and xanthochromic CSF: a case report.

Leptomeningeal spread with carcinomatous meningitis is a severe complication of glioblastoma, with a poor prognosis. Diagnosis is challenging, as the sensitivity of classic diagnostic investigations remains low for detecting cerebrospinal fluid (CSF) tumor spread and exclusion of infectious causes is mandatory, especially if unusual clinical findings are present. A 71-year-old woman was admitted to our hospital for recurrent episodes of high fever and xanthochromic meningitis, with subacute onset. Her past medical history was significant for a left temporal glioblastoma, treated with surgical resection and adjuvant chemo- and radiotherapy, with associated systemic immunosuppression secondary to chemotherapy. An extensive workup especially with molecular microbiology testing for exclusion of infectious causes was performed. CSF was analyzed for typical bacterial and viral causes, but also pathogens associated with immunosuppression, such as Listeria monocytogenes and Cryptococcus neoformans. A therapeutic trial of standard antituberculous drugs with repeated lumbar punctures were needed in order to exclude Mycobacterium tuberculosis and to confirm the diagnosis of carcinomatous meningitis by cytopathological examination of the CSF. The case describes an unusual clinical presentation of a patient with glioblastoma associated leptomeningeal dissemination, as high fever and xanthochromic CSF could raise important diagnostic and therapeutic challenges in the clinical practice. The diagnosis of carcinomatous meningitis requires an extensive workup for exclusion of infectious causes which is important for urgent oncologic treatment.

Mind the gap: IgG4-related disease mimicking infectious cerebral mass lesions

BackgroundCerebral intraparenchymal masses represent usually a neoplastic, or infectious differential diagnostic workup in neurology or infectious disease units.Case presentationOur patient was an 82-year-old male presenting with seizures, cerebral masses and a history of past treated pulmonary tuberculosis. Initial workup included a differential diagnosis of an infectious mass/multiple abscess. After exclusion of infectious or primary neoplastic origins by negative HIV serology, the absence of immune suppression, endocarditic lesions, negative results of blood cultures and bronchoalveolar lavage, negative cerebrospinal fluid workout on spinal tap led to exclusion of infectious causes. A surgical procedure was performed to access one of the lesions. This yielded a firm, cyst-like mass of histiocytic granulomatous tissue with a conspicuous plasmacellular component and a relevant IgG4 plasmacellular component consistent with IgG4-related disease.Steroid treatment determined conspicuous improvement and led to discharge of the patient.ConclusionParenchymal IgG4-related disease may be included as a new entity in the differential diagnosis of single or multiple cerebral masses in addition to infectious or neoplastic etiology.

Úlcera genital aguda em adolescente: caso clínico

Acute genital ulcer, also known as Lipschütz ulcer, is an uncommon, non-sexually transmitted condition characterized by the rapid onset of a necrotic and painful ulcer in the vulvar region. It occurs in adolescents and young women, with or without sexual activity. It may be preceded by influenza-like or mononucleosis-like symptoms. Acute genital ulcers have been associated with Epstein-Barr virus (EBV) infection or other viral or bacterial infections. However, in most cases, the cause is not determined. We report the clinical case of an 11-year-old girl without previous vaginal or oral ulceration without sexual contact who sought medical assistance with a rapidly progressive vulvar ulcer wich had started six days before, preceded by episodic low fever. The exclusion of infectious causes, the spontaneous healing of the lesion and the indeterminate serology for Epstein-Barr led to the diagnosis of ulcer of Lipschütz.

Phase II Trial of Natalizumab (Tysabri®) with Corticosteroids As Initial Treatment of Gastrointestinal Acute Graft Versus Host Disease

Background: Graft-vs.-host disease (GVHD) is caused by allorecognition of host antigens by tissue-specific donor lymphocytes. We have previously demonstrated that α4ß7 integrin is upregulated on both naïve and memory T cell subsets in patients who subsequently developed intestinal acute GVHD (Chen, BMT 2013). This integrin interacts with endothelial cell adhesion molecules and mediates homing of lymphocytes to the gastrointestinal (GI) tract. Natalizumab (Tysabri®, Biogen Inc.) is a selective adhesion molecule inhibitor, acting directly against the α4 subunit of α4 integrins. Given the poor outcomes of GI GVHD when treated with corticosteroids alone, we initiated a phase II study to determine the safety and efficacy of natalizumab in combination with corticosteroids for the initial treatment of acute GI GVHD.Methods: Subjects with new-onset, acute GVHD of the lower GI tract were eligible to participate. Other organ involvement was permitted but not required. Biopsy confirmation of GI GVHD and exclusion of infectious causes of diarrhea were required. Natalizumab was given at a dose of 300 mg IV, with a second dose permitted 4 weeks later in the event of an incomplete response. An initial corticosteroid dose of 2 mg/kg of methylprednisolone was suggested, but dosing and dose reductions were at the discretion of the treating physician. Steroids could be initiated up to 7 days prior to the initiation of natalizumab while biopsy and infectious disease specimens were being analyzed. The primary endpoint was GVHD-free survival rate 56 days from enrollment. Secondary endpoints included response rates at day 28 and 56, steroid dose at days 28, 56, 100, 180 and 365, incidence of systemic infections at day 56 and 180, and overall survival.Results: 18 subjects were enrolled and received at least one dose of natalizumab. Subjects had a median age of 63.5 years, and 12 were male. Fifteen had a non-myeloablative transplant, 12 had a matched unrelated donor, and all had received PBSCs. All subjects had newly diagnosed acute GI GVHD at time of enrollment; 4 had concomitant cutaneous and 1 had concomitant hepatic involvement. Stage 1, 2, 3, and 4 GI involvement was noted in 7, 4, 4, and 3 subjects respectively, corresponding to overall grade II GVHD in 7 and grade III in 11 subjects. Sixteen patients had data for response assessment. The day 56 GVHD-free survival rate was 37.5%. The overall response rate (PR+CR) for GI GVHD at day 28 and day 56 was 75% and 62.5% respectively. All surviving subjects except one achieved steroid dose reduction by day 56, with a median reduction of 61.6%. Three patients experienced treatment-related toxicity possibly related to natalizumab; one subject had grade 2 hepatic toxicity, one had grade 4 encephalopathy, and one developed hepatic failure. Three subjects have developed chronic GVHD. Four subjects had documented infections with bacteria (2), yeast (1), and viral pathogens (1- polyomavirus). Six subjects had measurable JC viremia prior to initiation of natalizumab and 8 subjects had measurable JC viremia at day 56, although only 1 subject had a viral load greater than 1000 copies/ml. No subject has developed JC-associated disease. Seven subjects have died. Causes of death include GVHD (2), disease relapse (2), and organ failure (3). With a median follow-up of 180 days, the 6 month overall survival was 52% (95% CI 25-74%).Conclusion: Natalizumab in combination with corticosteroids as initial treatment of acute gastrointestinal GVHD is feasible and well tolerated. These early results suggest a higher rate of response at day 56 than is typically observed with steroids alone. Inhibition of T-cell homing to the GI tract may improve GI GVHD response and potentially mitigate progression of acute GVHD. DisclosuresKoreth:Kadmon Corp: Membership on an entity's Board of Directors or advisory committees; Amgen Inc.: Consultancy; Prometheus Labs: Research Funding; Takeda Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Millennium Pharmaceuticals: Research Funding. Armand:Bristol-Myers Squibb: Consultancy, Research Funding; Tensha: Research Funding; Affimed: Research Funding; Sequenta/Adaptive: Research Funding; Merck & Co., Inc.: Consultancy, Research Funding; Roche: Research Funding; Genmab: Consultancy; Pfizer: Consultancy, Research Funding; Infinity: Consultancy; Otsuka: Research Funding; Sigma Tau: Research Funding. Antin:Gentium SpA/Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Cutler:Pfizer: Consultancy; Pharmacyclics: Consultancy; Kite: Consultancy; Bristol-Myers Squibb: Consultancy; Incyte: Consultancy; Astellas: Consultancy.

67 - Phase II Trial of Natalizumab (Tysabri®) with Corticosteroids as Initial Treatment of Gastrointestinal Acute Graft Versus Host Disease

Abstract Background: Graft-vs.-host disease (GVHD) is caused by allorecognition of host antigens by tissue-specific donor lymphocytes. We have previously demonstrated that α4s7 integrin is upregulated on both naive and memory T cell subsets in patients who subsequently developed intestinal acute GVHD (Chen, BMT 2013). This integrin interacts with endothelial cell adhesion molecules and mediates homing of lymphocytes to the gastrointestinal (GI) tract. Natalizumab (Tysabri®, Biogen Inc.) is a selective adhesion molecule inhibitor, acting directly against the α4 subunit of α4 integrins. Given the poor outcomes of GI GVHD when treated with corticosteroids alone, we initiated a phase II study to determine the safety and efficacy of natalizumab in combination with corticosteroids for the initial treatment of acute GI GVHD. Methods: Subjects with new-onset, acute GVHD of the lower GI tract were eligible to participate. Other organ involvement was permitted but not required. Biopsy confirmation of GI GVHD and exclusion of infectious causes of diarrhea were required. Natalizumab was given at a dose of 300 mg IV, with a second dose permitted 4 weeks later in the event of an incomplete response. An initial corticosteroid dose of 2 mg/kg of methylprednisolone was suggested, but dosing and dose reductions were at the discretion of the treating physician. Steroids could be initiated up to 7 days prior to the initiation of natalizumab while biopsy and infectious disease specimens were being analyzed. The primary endpoint was GVHD-free survival rate 56 days from enrollment. Secondary endpoints included response rates at day 28 and 56, steroid dose at days 28, 56, 100, 180 and 365, incidence of systemic infections at day 56 and 180, and overall survival. Results: 18 subjects were enrolled and received at least one dose of natalizumab. Subjects had a median age of 63.5 years, and 12 were male. Fifteen had a non-myeloablative transplant, 12 had a matched unrelated donor, and all had received PBSCs. All subjects had newly diagnosed acute GI GVHD at time of enrollment; 4 had concomitant cutaneous and 1 had concomitant hepatic involvement. Stage 1, 2, 3, and 4 GI involvement was noted in 7, 4, 4, and 3 subjects respectively, corresponding to overall grade II GVHD in 7 and grade III in 11 subjects. Sixteen patients had data for response assessment. The day 56 GVHD-free survival rate was 37.5%. The overall response rate (PR+CR) for GI GVHD at day 28 and day 56 was 75% and 62.5% respectively. All surviving subjects except one achieved steroid dose reduction by day 56, with a median reduction of 61.6%. Three patients experienced treatment-related toxicity possibly related to natalizumab; one subject had grade 2 hepatic toxicity, one had grade 4 encephalopathy, and one developed hepatic failure. Three subjects have developed chronic GVHD. Four subjects had documented infections with bacteria (2), yeast (1), and viral pathogens (1- polyomavirus). Six subjects had measurable JC viremia prior to initiation of natalizumab and 8 subjects had measurable JC viremia at day 56, although only 1 subject had a viral load greater than 1000 copies/ml. No subject has developed JC-associated disease. Seven subjects have died. Causes of death include GVHD (2), disease relapse (2), and organ failure (3). With a median follow-up of 180 days, the 6 month overall survival was 52% (95% CI 25-74%). Conclusion: Natalizumab in combination with corticosteroids as initial treatment of acute gastrointestinal GVHD is feasible and well tolerated. These early results suggest a higher rate of response at day 56 than is typically observed with steroids alone. Inhibition of T-cell homing to the GI tract may improve GI GVHD response and potentially mitigate progression of acute GVHD. Disclosures Koreth: Kadmon Corp: Membership on an entity's Board of Directors or advisory committees; Amgen Inc.: Consultancy; Prometheus Labs: Research Funding; Takeda Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Millennium Pharmaceuticals: Research Funding. Armand: Bristol-Myers Squibb: Consultancy, Research Funding; Tensha: Research Funding; Affimed: Research Funding; Sequenta/Adaptive: Research Funding; Merck & Co., Inc.: Consultancy, Research Funding; Roche: Research Funding; Genmab: Consultancy; Pfizer: Consultancy, Research Funding; Infinity: Consultancy; Otsuka: Research Funding; Sigma Tau: Research Funding. Antin: Gentium SpA/Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Cutler: Pfizer: Consultancy; Pharmacyclics: Consultancy; Kite: Consultancy; Bristol-Myers Squibb: Consultancy; Incyte: Consultancy; Astellas: Consultancy.

Atypical Kawasaki Disease in 2-Months Old Infant Presenting with Aseptic Meningitis

The diagnosis of incomplete or atypical Kawasaki disease (KD) is challenging. Children presenting with febrile illnesses may have few of the classical diagnostic criteria, yet develop clinical, laboratory and echocardiographic findings compatible with the condition. Early recognition and prompt treatment of KD is essential for better outcomes. This is particularly the case for infants who are at a greater risk of developing complications such as coronary artery aneurysms. This may be partly attributed to late diagnosis or initiation of therapy. This report discusses the case of a febrile infant with atypical Kawasaki disease presenting with aseptic meningitis and coronary artery aneurysm. The case highlights the importance of considering atypical Kawasaki disease in any infant with prolonged fever (more than seven days), following exclusion of infectious causes and in the absence of classical diagnostic criteria.

Cutaneous sarcoidosis: A rare case report

Sarcoidosis is a Greek word (Sarco means flesh and Eido means type or like). Cutaneous sarcoidosis occurs in up to one third of patients with systemic sarcoidosis. This disease is characterised by the presence of non - caseating epitheloid cell granulomas in the skin. Cutaneous sarcoidosis presents as a diagnostic challenge to the dermatopathologists due to its varied presentations and almost identical histologic pictures. Hence, exclusion of infectious causes and compatibility with clinical and radiologic picture serve as significant criteria to come up to a diagnosis. Sometimes; skin lesions are the first manifestation of systemic sarcoidosis. This is not a contagious or allergic disease. There is a risk of development of systemic manifestations at a later date; for which a close follow up is a must. We are presenting a case of cutaneous sarcoidosis, which later on progress to sarcoidosis with systemic manifestations.

Allergic proctocolitis: the clinical evolution of a transitory disease with a familial trend. Case reports

ABSTRACTAllergic colitis is a clinical manifestation of food allergy during the first months of life. It is estimated that genetic factors play a role in the expression of this allergic disease. This case report described the clinical progress of infants who were cousins from two distinct family groups with allergic colitis. Five infants under six months of age and of both sexes were studied, with a diagnosis of allergic colitis characterized clinically and histologically by (1) rectal bleeding; (2) exclusion of infectious causes of colitis; (3) disappearance of symptoms after elimination of cow's milk and dairy products from the child's and/or the mother's diet. Patients were submitted to the following diagnostic investigation: complete blood count; stool culture; parasitologic examination of stools; rectoscopy or colonoscopy; and rectal biopsy. Patient age varied from 40 days to six months; three were males. All patients presented with complaints of intense colic and rectal bleeding. The colonoscopy showed presence of hyperemia of the mucosa with microerosions and spontaneous bleeding upon the procedure. Microscopy revealed the existence of colitis with eosinophilia >20 e/HPF. Patients were treated with a hypoallergenic formula and showed remission of symptoms. After one year of age, all were submitted to an oral challenge with a milk formula and presented food tolerance. Allergic colitis is a disease with evident genetic inheritance and a temporary character.

Living with idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is the most common of the seven listed interstitial pneumonias in the American Thoracic Society/European Respiratory Society (ATS/ERS) consensus statement, and there is growing evidence that the incidence is increasing. Defined as a progressive fibrosing interstitial pneumonia of unknown cause, IPF is defined as being limited to the lungs and associated with histopathological and/or radiographical patterns consistent with usual interstitial pneumonia (UIP). A recent article by Navaratnam and colleagues documents the prevalence in UK to be around 15,000, with >5000 new cases per annum and unfortunately around 5000 deaths. With a median survival of 3–5 years after diagnosis, this is a devastating disease although the natural course of the disease varies, with some patients experiencing a steady decline over a few years, some experiencing a rapid decline, and others experiencing what appear to be similar to acute exacerbations in between relative periods of stability. Unlike the more common respiratory disorders such as chronic obstructive pulmonary disease (COPD) where patients are likely to die of other causes than the underlying COPD, those diagnosed with IPF will most often die from their disease process, estimated at around 60%, rather than with it and often during acute exacerbations. Mortality in patients with IPF increases with advancing age. Death rates are consistently higher in men than women, and there is seasonal variation, with the highest death rates occurring in the winter, even with the exclusion of infectious causes. If the cause of death is not attributable to an acute exacerbation of IPF, there are increased cardiovascular risks and an increased risk of venous thromboembolic disease which contribute to the cause of death. Other common causes of death in patients with IPF therefore include acute coronary syndromes, congestive heart failure, lung cancer, and infectious causes. Regrettably, late presentation often shortens the survival time of patients with IPF and there is often a delay of 1–2 years before presentation with symptoms and additionally there may be a problem with clinicians missing early clinical clues, although this will not alter the natural course of the disease process. The epidemiological origins and subsequent pathological developments of the process of IPF are still not completely understood, although the condition is believed to result from an inflammatory response to an unknown substance resulting in pathological scarring, and there may also be epidemiological and genetic factors. Whether the incidence and prevalence of IPF are influenced by geographic, ethnic, cultural, or racial factors is not yet clear. The ‘idiopathic’ nature of the disease meaning no cause can be found, can be particularly difficult to both understand and accept for those diagnosed. Although the disease occurs most often in people between 50 and 70 years of age, it can affect people of a younger age, and although the preponderance is in males, it is no respecter of gender. Unfortunately for people diagnosed with the condition, IPF is often a poorly understood condition with little knowledge and unfortunately no definitive treatment leaving people diagnosed with the disorder. Available information, for example, on the Internet can be distressing and documents lack of treatment and poor prognosis. Studies to date have yet to find robust evidence for any effective pharmacological treatment of IPF. Corticosteroids and other immunosuppressants are commonly tried treatments in IPF, although unfortunately ‘tried’ is the most important word here as there is little evidence that any of these are truly effective and the side effects can outweigh any potential benefit. Any decision to attempt to treat IPF needs an open and honest discussion with patients and their views taken

Presenilin-1 mutation associated with amnesia, ataxia, and medial temporal lobe T2 signal changes

In the correct clinical context, an important cause of medial temporal MRI signal abnormality is herpes simplex encephalitis. In more subacute presentations, autoimmune or paraneoplastic limbic encephalitis are common etiologies. We present a man with subacute onset of memory impairment and gait ataxia whose MRI was suggestive of limbic encephalitis. After exclusion of infectious causes, immunosuppression was started. He eventually proved to have Alzheimer disease (AD) due to the S170F mutation in the presenilin 1 (PS-1) gene. ### Case report. A 34-year-old welder presented to our neurology department with memory impairment and unsteadiness. His work colleagues reported a few months' history of frequently loosing his tools and difficulties with his balance. When examined he was disorientated in time and he had no recall of a name and address after a 5-minute delay. There was head titubation, truncal, mild finger-nose, and gait ataxia. Diadochokinesis was poor bilaterally. Otherwise the examination was normal. MRI showed generalized cerebral (figure e-1 on the Neurology ® Web site at www.neurology.org) and cerebellar atrophy, increased signal from both hippocampi and amygdalae …

Minocycline-induced hypersensitivity syndrome presenting with meningitis and brain edema: a case report

BackgroundHypersentivity Syndrome (HS) may be a life-threatening condition. It frequently presents with fever, rash, eosinophilia and systemic manifestations. Mortality can be as high as 10% and is primarily due to hepatic failure. We describe what we believe to be the first case of minocycline-induced HS with accompanying lymphocytic meningitis and cerebral edema reported in the literature.Case presentationA 31-year-old HIV-positive female of African origin presented with acute fever, lymphocytic meningitis, brain edema, rash, eosinophilia, and cytolytic hepatitis. She had been started on minocycline for inflammatory acne 21 days prior to the onset of symptoms. HS was diagnosed clinically and after exclusion of infectious causes. Minocycline was withdrawn and steroids were administered from the second day after presentation because of the severity of the symptoms. All signs resolved by the seventh day and steroids were tailed off over a period of 8 months.ConclusionClinicians should maintain a high index of suspicion for serious adverse reactions to minocycline including lymphocytic meningitis and cerebral edema among HIV-positive patients, especially if they are of African origin. Safer alternatives should be considered for treatment of acne vulgaris. Early recognition of the symptoms and prompt withdrawal of the drug are important to improve the outcome.

Oral chronic GVHD in children—treatment with topical tacrolimus ointment

Oral chronic graft versus host disease (GVHD) frequently presents as lichen-type changes, hyperkeratotic plaques, pseudomembranes, or decreased oral range of motion in patients with sclerotic features of skin GVHD and is often associated with significant limitations of oral food intake and a generally decreased quality of life. Decreased oral intake is especially problematic in children with already reduced caloric uptake due to chronic gastrointestinal GVHD. Systemic tacrolimus is well established and efficacious for prophylaxis and treatment of acute and chronic GVHD and topical tacrolimus has shown activity in chronic GVHD skin lesions. We therefore initiated a pilot study to investigate the safety and efficacy of topical tacrolimus ointment in pediatric stem cell transplant recipients with debilitating oral chronic GVHD. Two patients (6 and 13 years) with β-thalassemia were included in the study at 179 and 382 days post transplant respectively. Both suffered from progressive onset, moderate to severe chronic GVHD with involvement of the oral mucosa exhibiting lichen-type changes alongside pain, erythema and small ulcerations of the oral mucosa. One patient additionally presented with progressive sclerosis of the lips limiting opening of the oral cavity. In both patients oral lesions had been refractory to systemic GVHD treatment (cyclosporine 3 and 2 mg/kg respectively). After exclusion of infectious causes for oral lesions, tacrolimus ointment 0.1% (Protopic®, Fujisawa Healthcare) was applied twice daily using a sterile gauze that was inserted into both buccal pouches and left in place for 20 minutes without rinsing the mouth afterwards. At a follow up of 24 and 14 weeks respectively, the only side effect observed was a slight burning discomfort after the first application in one patient. Tacrolimus was absorbed in both patients as exhibited by tacrolimus plasma levels up to 4.2 and 5.6 ng/ml respectively. Pain, erythematous lesions and ulcerations disappeared within 4 weeks of treatment in both. Lichenoid changes markedly improved in both and range of oral opening normalized in the patient affected. Systemic immunosuppression was tapered during treatment with topical tacrolimus in both patients. We conclude that topical application of tacrolimus ointment holds promise as a safe and efficacious treatment for oral chronic GVHD in children. These findings deserve to be affirmed in a larger prospective evaluation. Oral chronic graft versus host disease (GVHD) frequently presents as lichen-type changes, hyperkeratotic plaques, pseudomembranes, or decreased oral range of motion in patients with sclerotic features of skin GVHD and is often associated with significant limitations of oral food intake and a generally decreased quality of life. Decreased oral intake is especially problematic in children with already reduced caloric uptake due to chronic gastrointestinal GVHD. Systemic tacrolimus is well established and efficacious for prophylaxis and treatment of acute and chronic GVHD and topical tacrolimus has shown activity in chronic GVHD skin lesions. We therefore initiated a pilot study to investigate the safety and efficacy of topical tacrolimus ointment in pediatric stem cell transplant recipients with debilitating oral chronic GVHD. Two patients (6 and 13 years) with β-thalassemia were included in the study at 179 and 382 days post transplant respectively. Both suffered from progressive onset, moderate to severe chronic GVHD with involvement of the oral mucosa exhibiting lichen-type changes alongside pain, erythema and small ulcerations of the oral mucosa. One patient additionally presented with progressive sclerosis of the lips limiting opening of the oral cavity. In both patients oral lesions had been refractory to systemic GVHD treatment (cyclosporine 3 and 2 mg/kg respectively). After exclusion of infectious causes for oral lesions, tacrolimus ointment 0.1% (Protopic®, Fujisawa Healthcare) was applied twice daily using a sterile gauze that was inserted into both buccal pouches and left in place for 20 minutes without rinsing the mouth afterwards. At a follow up of 24 and 14 weeks respectively, the only side effect observed was a slight burning discomfort after the first application in one patient. Tacrolimus was absorbed in both patients as exhibited by tacrolimus plasma levels up to 4.2 and 5.6 ng/ml respectively. Pain, erythematous lesions and ulcerations disappeared within 4 weeks of treatment in both. Lichenoid changes markedly improved in both and range of oral opening normalized in the patient affected. Systemic immunosuppression was tapered during treatment with topical tacrolimus in both patients. We conclude that topical application of tacrolimus ointment holds promise as a safe and efficacious treatment for oral chronic GVHD in children. These findings deserve to be affirmed in a larger prospective evaluation.