Treatment of enteritis in chronic granulomatous disease with granulocyte colony stimulating factor

Background—In several diseases there is a relationbetween deficiency of neutrophil granulocytes and granulomatouslesions. Recently, in glycogen storage disease type Ib, this relationhas been supported by the beneficial effect of treatment of enteritis with granulocyte-macrophage colony stimulating factor.
Aim—To investigate whether chronic granulomatousdisease could be treated according to the same principle.
Patients and methods—Inflammatory lesions weremonitored in two brothers with chronic granulomatous diseasedemonstrated by very low superoxide production in neutrophilgranulocytes. The two patients were treated with recombinant humangranulocyte colony stimulating factor on three occasions when thedisease was active.
Results—In one patient, remission of an inflamedstenosis of the colon sigmoideum was shown by granulocytescintigraphy after one month of treatment with granulocyte colonystimulating factor. In the other patient, remission of colon diseaseand later of a non-malignant tumour in the right lung hilum was shownby colonoscopy and computed tomography scans respectively.
Conclusion—Remission of inflammatory lesions intwo brothers with chronic granulomatous disease was induced bygranulocyte colony stimulating factor on three occasions. The mechanismfor this effect is not known. The result is similar to the response found in patients with leucocyte deficiency due to glycogen storage disease type Ib.

Keywords:chronic granulomatous disease; enteritis; granulocyte colony stimulating factor

     

Pathogenesis of liver injury in Takayasu arteritis: advanced understanding leads to new horizons

Liver injury in Takayasu arteritis (TA) is a rare phenomenon. Most symptoms are nonspecific, and the exact pathogenesis remains to be elucidated. Early diagnosis and new treatment methods are important for an improved prognosis. A summary of the clinical information and mechanistic analyses may contribute to making an early diagnosis and development of new treatment methods. A PubMed search was conducted using the specific key words “Takayasu arteritis” and “liver” or “hepatitis” or “hepatic”. Symptoms and treatment of TA with an accompanying liver injury were reviewed retrospectively. Many factors are presumed to be involved in the mechanism of TA with liver injury, including the immune response, genes, infections, and gut microbiota. There are several lines of evidence indicating that immune dysfunction is the main pathogenic factor that triggers granuloma formation in TA patients. However, the role of genetics and infections has not been fully confirmed. Recently, the gut microbiota has emerged as an essential component in the process. We reviewed in detail the current concepts that support the complex pathogenesis of TA accompanied by liver injury, and we presented recent theories from the literature. Finally, we discussed future research directions of liver injury in TA.     

Hemophagocytic lymphohistiocytosis and primary immune deficiency disorders

Hemophagocytic lymphohistiocytosis (HLH) is characterized by uncontrolled immune activation and is traditionally associated with inherited gene defects or acquired causes. In addition to abnormalities in cytotoxic granules and lysosomes, various primary immune deficiency disorders (PID) have been identified among patients suffering from HLH. Our purpose was twofold: to better characterize and detail the association between PID and HLH.     

An autopsy case of Balamuthia mandrillaris amoebic encephalitis,a rare emerging infectious disease,with a brief review of the cases reported in Japan

Balamuthia mandrillaris is an amoeba found in fresh water and soil that causes granulomatous amoebic encephalitis. We report herein an autopsy case of B. mandrillaris amoebic encephalitis, which was definitely diagnosed by PCR. An 81‐year‐old man, who had Sjögren's syndrome, manifested drowsiness 2 months before his death with progressive deterioration. Neuroimaging demonstrated foci of T2‐ and fluid‐attenuated inversion recovery high and T1 low‐intensity with irregular post‐contrast ring enhancement in the cerebral hemisphere, thalamus and midbrain. Pathologically, multiple hemorrhagic and necrotic lesions were found in the cerebrum, thalamus, midbrain, pons, medulla and cerebellum, which were characterized by liquefactive necrosis, marked edema, hemorrhage and necrotizing vasculitis associated with the perivascular accumulation of amoebic trophozoites, a few cysts, and the infiltration of numerous neutrophils and microglia/macrophages. The trophozoites were ovoid or round, 10–60 μm in diameter, and they showed foamy cytoplasm and a round nucleus with small karyosome in the center. The PCR and immunohistochemistry from paraffin‐embedded brain specimens revealed angioinvasive encephalitis due to B. mandrillaris. Human cases of B. mandrillaris brain infection are rare in Japan, with only a few brief reports in the literature.     

A granulomatous conundrum: Concurrent necrobiosis lipoidica,cutaneous sarcoidosis and erythema nodosum in a nondiabetic patient

Necrobiosis lipoidica (NL) and cutaneous sarcoidosis are granulomatous disorders with a largely unknown aetiopathogenesis. Evidence of co‐existing NL and sarcoidosis in the same patient may suggest a degree of overlap between these entities through shared granulomatous inflammatory pathways. Occasionally, one condition can mimic the other, making their distinction difficult. We report a novel case of a non‐diabetic woman who presented with concurrent NL, cutaneous sarcoidosis and erythema nodosum. We discuss some of the complexities distinguishing these entities and propose that they may represent different stages of the same granulomatous process linked through yet unknown pathomechanisms.     

Respiratory complications after haematopoietic stem cell transplantation in a patient with chronic granulomatous disease

summary .  Chronic granulomatous disease (CGD) is an inherited immunodeficiency disorder caused by defects in NADPH oxidase and characterized by recurrent life-threatening bacterial and fungal infections. Although CGD has been considered to be a target for gene therapy, bone marrow transplantation (BMT) is now selected as the radical treatment in most cases. We performed BMT in a patient with CGD with severe infections and experienced respiratory complications of diffuse alveolar haemorrhage and/or infection-associated alveolar haemorrhage. We suggest that attention be paid to signs of onset of alveolar haemorrhage during BMT in CGD patients.     

Autosomal recessive chronic granulomatous disease associated with 18q- syndrome and end-stage renal failure due to Henoch-Schönlein nephritis

Chronic granulomatous disease (CGD) is an inherited disorder in which phagocytes, including polymorphonuclear neutrophils, are unable to generate oxygen-derived microbicidal compounds, among them superoxide [1]. Two main types of CGD are known, an X-linked form which is normally associated with the absence of cytochromeb ₅₅₈, a component of the membrane-associated reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase which generates superoxide and an autosomal recessive form, in which cytochromeb ₅₅₈ is present, caused by the deficiency of a cytosolic factor required to activate NADPH oxidase [4]. Patients with the X-linked type are highly susceptible to infections; those with the autosomal recessive form may be less severely affected [10]. We report the unusual association of autosomal CGD with 18q- syndrome in a girl who developed terminal renal insufficiency caused by Henoch-Schönlein nephritis, and speculate on the possibility that the gene defect of autosomal recessive CGD may be located on chromosome 18.