Severe thrombocytosis and anemia associated with celiac disease in a young female patient: a case report

Introduction

Platelet counts exceeding 1.000 × 10³/μl are usually considered secondary to another cause, particularly to chronic myeloproliferative disease (CMPD). Reactive thrombocytosis due to iron deficiency rarely exceeds platelet counts of 700 × 10³/μl.

Case presentation

Here we report the case of a young woman presenting with clinical signs of severe anemia. Laboratory findings confirmed an iron-deficiency anemia associated with severe thrombocytosis of 1703 × 10³/μl. Macroscopic gastrointestinal and genitourinary tract bleeding was excluded. The excessive elevation of platelets, slightly elevated lactate dehydrogenase and slightly elevated leukocytes along with the absence of other inflammation parameters raised the suspicion of an underlying hematological disease. However, bone marrow evaluation could not prove the suspected diagnosis of a CMPD, especially essential thrombocythemia (ET). In the further clinical course the platelet count returned to normal after raising the hemoglobin to a level close to normal range with erythrocyte transfusion, and normalization of serum iron and decline of erythropoietin. Finally, following small bowel biopsy, despite the absence of typical clinical signs, celiac disease was diagnosed. After discharge from hospital the patient was commenced on a gluten-free diet and her hemoglobin almost completely normalized in the further follow-up period.

Conclusion

This case illustrates the rare constellation of an extreme thrombocytosis most likely secondary to iron deficiency due to celiac disease. This represents, to the best of the authors' knowledge, the highest reported platelet count coincident with iron deficiency. A potential mechanism for the association of iron-deficiency anemia and thrombocytosis is discussed. Even in the presence of 'atypically' high platelets one should consider the possibility of reactive thrombocytosis. Extreme thrombocytosis could emerge in the case of iron deficiency secondary to celiac disease.

     

Munc18 plays an important role in the regulation of glutamate release during female puberty onset

Munc18, a mammalian homolog of C. elegans Unc, is essential for neurotransmitter release. The aim of this study was to identify estrogen-dependent expression of Munc18-1 and its role in the regulation of glutamate release for puberty onset. Hypothalamic munc18-1 mRNA levels were significantly increased by estrogen treatment in ovariectomized, immature female rats. During pubertal development, the munc18-1 mRNA levels dramatically increased between the juvenile period and the anestrous phase of puberty. Intracerebroventricular administration of an antisense oligodeoxynucleotide against munc18-1 mRNA significantly decreased glutamate release and delayed the day of puberty onset. These results suggest that Munc18-1, expressed in an estrogen-dependent manner, plays an important role in the onset of female puberty via the regulation of glutamate release.     

Romanian experience in child celiac disease diagnosis

Last consensus in celiac disease in 2008 conducted under the aegis of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition jointly with North American Society of Pediatric Gastroenterology, Hepatology and Nutrition reveals the following: "celiac disease is a chronic immune-mediated enteropathy characterized by sensitization to gluten. That can affect any organ or system, with a wide range of clinical manifestations of variable severity". Thus, in recent years, clinical picture of celiac disease has changed the old paradigm--bowel disease with villous atrophy and malnutrition, being replaced with the new paradigm--multi-organ autoimmune disease, affecting many organs and systems throughout but with more less specific symptoms, which undiagnosed leads to delayed diagnosis, at a late-onset disease and long-term major complications as the risk of cancer. According to this consensus "the serological diagnosis of celiac disease is based on high sensitivity and specificity tests", but in line with changing clinical features of celiac disease, its diagnosis has undergone significant changes in recent years. These changes in the diagnosis of celiac disease, we have decided to analyze them.     

Delayed puberty in lambs chronically treated with oestradiol

Intact female lambs were chronically treated with low levels of oestradiol by Silastic implant from 20 weeks of age. Reproductive cycles were initiated in only 33% of these lambs (3 of 9) compared to 80% of untreated females (11 of 14) by 45 weeks when the study was terminated. Moreover, in the 3 oestradiol-treated lambs which began cycles, the age at first oestrus was delayed 3 weeks (37 +/- 1 weeks of age vs 34 +/- 1 weeks of age for untreated controls). Retardation of the pubertal process was not due to absence of the pubertal rise in circulating LH. At about 32 weeks of age, chronic oestradiol treatment was no longer able to suppress tonic LH secretion and serum LH increased in intact, oestradiol-treated lambs. These results indicate that a maturational decrease in responsiveness to oestradiol inhibition of tonic LH secretion can be demonstrated in the intact female, as in the ovariectomized female. However, chronic oestradiol suppression of prepubertal LH secretion also delays onset of reproductive cycles. This finding raises the possibility that low tonic LH secretion, presumably in the form of slow pulses, is necessary for development or maintenance of ovarian function before puberty. In the absence of LH during the last part of sexual maturation, the ability of the ovary to respond to the high frequency LH pulses during the pubertal gonadotrophin rise may be delayed.     

Aggressive Burkitt-like lymphoma of colon in a patient with prior celiac disease

Background: Celiac disease (CD) and immunosuppression are the two risk factors for gastrointestinal, as well as non-gastrointestinal, non-Hodgkin’s lymphomas (NHL). Recent large retrospective studies confirm that celiac disease significantly increases risk of developing small bowel lymphomas by 30 to 40 percent and other gut malignancies by 83-fold. Case Report: A 75-year-old man with a history of CD of two-year duration presented with pallor, fatigue, and 20-pound weight loss of three weeks duration. There was a vague non-tender mass in the right hypochondrium, and his stools tested positive for occult blood. The lab values were within normal range, except for hemoglobin of 11mg/dL, MCV 75, mildly elevated SGOT of 61 IU/L, and LDH of about 5000 IU/L. Work-up including computerized tomography (CT) scan, positron emission tomography (PET) scan, and colonoscopy were performed. Results: A CT scan of the abdomen showed extensive carcinomatosis, scattered lymphadenopathy, and small pleural effusions. PET scan results coincided with CT findings. Colonoscopy revealed a friable nodular mass in the hepatic flexure, histopathology of which confirmed a high-grade B-cell lymphoma. Flow cytometry following immunostaining was positive for CD10, CD19, CD20, CD45, CD79a, and Ki-67. FISH assay demonstrated t (14:18) translocation and bcl-2 rearrangement. The bone marrow biopsy showed evidence of disease. The patient was treated with rituximab, plus cyclophosphamide, Adriamycin, vincristine, and prednisone (CHOP-R), with intrathecal methotrexate prophylaxis. Currently, the patient remains in remission. Conclusion: This is the first case of aggressive Burkitt-like lymphoma (BLL) occurring in a patient with celiac disease in his eighth decade of life. It is possible that chronic inflammation, profound immunosuppression, and nutritional deficit could lead to development of high-grade B-cell lymphoproliferative disorders. Further molecular studies are warranted to the investigate the link between certain polymorphisms of human leukocyte antigens (HLA) in B-cell populations in the gut, and this might be useful to identify high-risk individuals in the population of patients with CD.     

Acute watery diarrhea as the initial presenting feature of a pheochromocytoma in an 84-year-old female patient

We report the case of an 84-year-old woman who was initially admitted to the emergency room of our institution for frank dehydration caused by acute and severe secretory diarrheas along with acidosis and hypokalemia. After extensive gastrointestinal investigations, the etiology of the diarrhea remained unclear. Because clinical symptoms and ionogram parameters worsened, despite intravenous fluids and electrolyte replacement, an abdominal CT scan was performed and unexpectedly revealed a 4.5-cm mass in the right adrenal gland. Several separate 24-hour urine catecholamines were shown to be highly elevated. The diagnosis of pheochromocytoma was confirmed by MIBG scintigraphy and MRI. Before the admission, the patient never experienced symptoms suggestive of pheochromocytoma, except dry mouth and fear of impending death on several occasions. After 2 weeks, the diarrhea stopped abruptly and spontaneously without specific medication but after adequate rehydration. The patient subsequently underwent surgical removal of the adrenal medullary mass. Postoperatively, urinary catecholamines returned to normal values. Immunohistochemical study of the tumor confirmed the diagnosis of pheochromocytoma and revealed the presence of VIP-positive cells organized as islets in scattered areas of the tissue. This case illustrates the protean mode of presentation of pheochromocytoma, as well as the ability of medullary neural crest-derived cells to produce various neuropeptides potentially responsible for a large variety of symptoms.     

A 70-year-old man with isolated weight loss and a pellagra-like syndrome due to celiac disease

An elderly man was diagnosed with celiac disease, which presented with three notable features: first, presentation at the age of 70 with no prior gastrointestinal symptomatology or positive family history; second, triggering of all symptoms following recent myocardial infarction and infective endocarditis; third, presentation with marked (more than 20 percent) weight loss and pellagra-like skin lesions despite nearly normal examination and laboratory tests. Thus, celiac disease may present as a pellagra-like syndrome in the elderly with predominant weight loss that is enhanced by the related taste disturbances.     

The role of monoamines in female puberty

The estradiol positive feedback mechanism appears to become mature between days 10 and 20 after birth. Rising serum prolactin levels between day 20 after birth and puberty are correlated with high hypothalamic norepinephrine turnover. High prolactin levels stimulate hypothalamic dopamine (DA) turnover, which may actively inhibit hypothalamic luteinizing hormone-releasing hormone (LHRH) release. Hypothalamic DNA receptor sensitivity is high in 10- to 20-day-old rats and gradually decreases between day 20 after birth and puberty. The reason for this desensitization may be the high hypothalamic DA turnover. This may result in a less strong inhibition of LHRH release allowing the positive feedback action of estradiol to elicit the first preovulatory luteinizing hormone (LH) surge initiating puberty.     

A new mutation in exon 7 of NEMO gene: late skewed X-chromosome inactivation in an incontinentia pigmenti female patient with immunodeficiency

Incontinentia pigmenti is an X-linked genodermatosis, lethal in males. Affected females survive because of X-chromosome dizygosity and negative selection of cells carrying the mutant X-chromosome, and for this reason the skewed X inactivation pattern is often used to confirm the diagnosis. The most frequent mutation is a deletion of part of the NEMO gene (NEMOΔ4–10), although other mutations have been reported. Mutations of NEMO which do not abolish NF-κB activity totally permit male survival, causing an allelic variant of IP called hypohidrotic ectodermal dysplasia and immunodeficiency (HED-ID). We present a non-classical IP female patient who also suffered transient immunodeficiency because of a late and progressive selection against peripheral blood cells carrying an active mutated X-chromosome. This finding suggests that in the absence of known mutation the X-inactivation studies used in genetic counselling can induce mistakes with some female patients. At the age of 3 years and 6 months, all immunodeficiency signs disappeared, and the X-chromosome inactivation pattern was completely skewed. The low T cell proliferation and CD40L expression corroborate the important role of NEMO/ NF-κB pathway in T cell homeostasis. The decreased NEMO protein amount and the impaired IkBα degradation suggest that this new mutation, NM_003639: c.1049dupA, causes RNA or protein instability. To our knowledge, this is the first time that selection against the mutated X-chromosome in X-linked disease has been documented in vivo.     

Delayed diagnosis of symptomatic coronary artery disease in young men

Delay in making the diagnosis of symptomatic coronary artery disease was determined by studying the medical histories of 265 men aged 24.7 to 49.9 (mean 40.1) years with angiographically proven obstructive coronary atherosclerosis. The diagnosis of angina pectoris was delayed three times as often as the diagnosis of myocardial infarction, and for five times as long. The diagnosis of symptomatic coronary artery disease was delayed three and a half times more often in patients less than 35 years of age, than in patients over 45; the average time from presentation with symptoms to diagnosis was 30 times longer in patients under 35 years of age than in patients over 45.     

Recent advances in biosensors for diagnosis of celiac disease: A review

Celiac disease (CD) is an intestinal issue activated by the inappropriate immune reaction towards gluten protein of wheat, rye, barley, oats, and autoantigen, tissue transglutaminase. Regardless of the accessibility of immunochemical conventions for research facility analysis of CD, there is as yet a need of speedier, less expensive, and simpler devices for diagnosing CD. This review concentrates on progresses in biosensors for diagnosing CD in perspective of the scaled down hardware, multianalyte discovery and low sample volume necessity. Various recently developed biosensors in this field are presented.     

Correctness of diagnosis of celiac disease based on personal data]

A way of coeliac disease diagnosis was assessed in 348 children, Only 14% of patients has been examined according to ESPGAN recommendations and in the proper time. Diagnosis has been completed in 123 patients, and coeliac disease has been diagnosed only in 38 of them. The I biopsy has not been performed in 96 children, the II biopsy--in 136 children, gluten-free diet has not been observed in 105 children after the I biopsy. Other causes of diagnostic failures included: prolongation of the consecutive stages and improper histological evaluation, change of biopsies order, erroneous clinical evaluation. Diagnosis according to ESPGAN recommendations is practically very difficult and time consuming. Immunological markers of coeliac disease (IgA EmA, ARA) should lead to simplification and adjustment of those recommendations in Poland.     

Effects of exposure to an estrual female on the attainment of puberty in gilts

A total of 304 prepubertal gilts were randomly allocated to 4 treatment groups across 10 replications for a 50 d treatment period beginning at 170 d of age. The 4 treatment groups consisted of: 1) Gilts that were continuously exposed to one of a group of older, ovariectomized females that had been treated with 2 mg/ml estradiol benzoate to stimulate estrus (SE); 2) Gilts that were continuously exposed to an older, anestrous, ovariectomized female (OVX); 3) Gilts that were exposed to a mature boar for 15 min/d (BE); 4) Gilts that were isolated from any direct physical contact with other pigs (C). A gilt was considered to have attained puberty when she exhibited a standing reflex when mounted by the boar (BE group only) or to pressure applied manually to the back or had plasma progesterone concentrations > 2 ng/ml for 2 consecutive weeks. Data were analyzed as a randomized complete block design with treatment and replication in the model. A higher percentage of gilts attained puberty in the BE group than in the 3 other groups (52 vs 26, 30 and 32%, BE vs SE, OVX and C, respectively; P = 0.002). Gilts exposed to an estrual female or a mature boar attained puberty sooner after treatment was initiated than gilts in other treatment groups (12.6 and 17.8 vs 26.7 and 24.1 d, SE and BE vs OVX and C, respectively; P = 0.0003). Of the gilts attaining puberty during the experimental period, the highest percentage of gilts exhibited estrus within 10 d of treatment in the SE group (55.0 vs 26.1, 37.8 and 16.7%, BE vs SE, OVX and C, respectively; P = 0.05). Age at puberty was also lower SE or BE than OVX or C groups (176.3 and 181.0 vs 189.4 and 188.1 d, respectively; P = 0.0001). Weight at puberty was unaffected by treatment. These results suggest that exposure to an estrual female was effective in stimulating peripubertal females to express estrus, thus reducing the age at puberty. Boar exposure had a stimulatory effect not only at the initiation of exposure but throughout the experimental period, resulting in a higher percentage of gilts attaining puberty.