Proposal Of Diagnostic Criteria Research Articles

Intercritical photophobia in the migrainous patient. Proposal for diagnostic criteria

IntroductionPhotophobia is a symptom of abnormal light intolerance without pain sensation that requires an anamnesis and an examination to diagnose an underlying etiology. Basic procedureThis article focuses on 30 clinical cases with isolated intense photophobia and on the review of the literature. ObjectiveThe purpose of this article is to establish diagnostic criteria for photophobia. ResultsThe etiology of photophobia appears to be at the level of the intrinsically photosensitive retinal ganglion cells known as melanopsin cells and at a neurochemical level mediated by calcitonin-related peptide and the pituitary activating peptide cyclase. ConclusionThe treatment of photophobia could consist of monoclonal antibodies against calcitonin-related peptide and/or pituitary activating peptide cyclase.

Frequency, signs and symptoms, and criteria adopted for long COVID-19: A systematic review.

AimsTo identify, systematically evaluate and summarise the best available evidence on the frequency of long COVID‐19 (post‐acute COVID‐19 syndrome), its clinical manifestations, and the criteria used for diagnosis.MethodsSystematic review conducted with a comprehensive search including formal databases, COVID‐19 or SARS‐CoV‐2 data sources, grey literature, and manual search. We considered for inclusion clinical trials, observational longitudinal comparative and non‐comparative studies, cross‐sectional, before‐and‐after, and case series. We assessed the methodological quality by specific tools based on the study designs. We presented the results as a narrative synthesis regarding the frequency and duration of long COVID‐19, signs and symptoms, criteria used for diagnosis, and potential risk factors.ResultsWe included 25 observational studies with moderate to high methodological quality, considering 5440 participants. The frequency of long COVID‐19 ranged from 4.7% to 80%, and the most prevalent signs/symptoms were chest pain (up to 89%), fatigue (up to 65%), dyspnea (up to 61%), and cough and sputum production (up to 59%). Temporal criteria used to define long COVID‐19 varied from 3 to 24 weeks after acute phase or hospital discharge. Potentially associated risk factors were old age, female sex, severe clinical status, a high number of comorbidities, hospital admission, and oxygen supplementation at the acute phase. However, limitations related to study designs added uncertainty to this finding. None of the studies assessed the duration of signs/symptoms.ConclusionThe frequency of long COVID‐19 reached up to 80% over the studies included and occurred between 3 and 24 weeks after acute phase or hospital discharge. Chest pain, fatigue, dyspnea, and cough were the most reported clinical manifestations attributed to the condition. Based on these systematic review findings, there is an urgent need to understand this emerging, complex and challenging medical condition. Proposals for diagnostic criteria and standard terminology are welcome.

Congestive nephropathy: a neglected entity? Proposal for diagnostic criteria and future perspectives.

Venous congestion has emerged as an important cause of renal dysfunction in patients with cardiorenal syndrome. However, only limited progress has been made in differentiating this haemodynamic phenotype of renal dysfunction, because of a significant overlap with pre‐existing renal impairment due to long‐term hypertension, diabetes, and renovascular disease. We propose congestive nephropathy (CN) as this neglected clinical entity. CN is a potentially reversible subtype of renal dysfunction associated with declining renal venous outflow and progressively increasing renal interstitial pressure. Venous congestion may lead to a vicious cycle of hormonal activation, increased intra‐abdominal pressure, excessive renal tubular sodium reabsorption, and volume overload, leading to further right ventricular (RV) stress. Ultimately, renal replacement therapy may be required to relieve diuretic‐resistant congestion. Effective decongestion could preserve or improve renal function. Congestive acute kidney injury may not be associated with cellular damage, and complete renal function restoration may be a confirmatory diagnostic criterion. In contrast, a persistently low renal perfusion pressure might induce renal dysfunction and histopathological lesions with time. Thus, urinary markers may differ. CN is mostly seen in biventricular heart failure but may also occur secondary to pulmonary arterial hypertension and elevated intra‐abdominal pressure. An increase in central venous pressure to >6 mmHg is associated with a steep decrease in glomerular filtration rate. However, the central venous pressure range that can provide an optimal balance of RV and renal function remains to be determined. We propose criteria to identify cardiorenal syndrome subgroups likely to benefit from decongestive or pulmonary hypertension‐specific therapies and suggest areas for future research.

Key histopathologic features in idiopathic noncirrhotic portal hypertension: an interobserver agreement study and proposal for diagnostic criteria.

Histologic features of idiopathic noncirrhotic portal hypertension (INCPH), loosely termed as obliterative portal venopathy (OPV), are heterogenous, often subtle, and overlap with other entities. To this date, no consensus histopathologic diagnostic criteria have been established for INCPH. For these reasons, rendering a reproducible consensus histologic diagnosis of OPV on a liver biopsy may often be challenging even for experienced hepatopathologists. We report herein a two-phase interobserver agreement study on the diagnosis of OPV and assessed the relative value of histologic features in 104 liver biopsies in distinguishing between INCPH and non-INCPH with the goal to obtain a consensus on specific practical diagnostic criteria. Six hepatopathologists blinded to clinical information and original pathologic diagnosis reviewed internet-based case study sets with high-resolution whole-slide images. The initial interobserver agreement on OPV was expectedly low, but significantly improved (moderate agreement in most categories) upon adopting a consensus view recognizing portal vein sclerosis as the only strong independent histologic predictor for INCPH, and that contrary to the conventional view, aberrant portal/periportal vessels does not significantly contribute to the positive assignment of OPV status. We propose a three-tiered classification with diagnostic criteria to facilitate the histologic assignment of OPV status for the evaluation of INCPH. Furthermore, we have validated the performance of the proposed criteria either based on histology alone or coupled with clinicopathologic correlation. This classification may aid in practical histologic assessment of liver biopsies with or without portal hypertension and help to improve diagnostic consistency and accuracy.

An evaluation of food addiction as a distinct psychiatric disorder.

To evaluate the state of the literature for whether food addiction may warrant consideration as a distinct psychiatric disorder in the Diagnostic and Statistical Manual (DSM) using Blashfield et al.'s (1990; Comprehensive Psychiatry, 31(1), 15-19) five criteria. This framework was utilized because it has recently been applied to examine the diagnostic utility of several eating disorder phenotypes. The criteria are: (a) at least 50 journal articles published on the proposed syndrome in the past 10 years; (b) proposal of diagnostic criteria and assessment measures; (c) clinician reliability in diagnosis; (d) cohesiveness of the proposed diagnostic criteria; and (e) differentiation from similar, existing diagnostic categories. For each criterion, a literature review was conducted to examine if the minimum qualification had been met, and key findings were discussed. Two of the criteria (literature and differentiation) have been empirically supported to extent specified. Two criteria (diagnostic criteria and syndrome) have been partially fulfilled, due to only having self-report assessment measures and no examination of the odds ratios for meeting more than one symptom, respectively. Clinician reliability has not yet been evaluated. The existing literature suggests that food addiction may warrant consideration as a proposed diagnostic category in the DSM, though future research is needed to fulfill Blashfield et al.'s (1990; Comprehensive Psychiatry, 31(1), 15-19) criteria. The development of a semi-structured interview would be an impactful contribution for addressing these gaps.

Progress in perceptual research: the case of prosopagnosia.

Prosopagnosia is an impairment in the ability to recognize faces and can be acquired after a brain lesion or occur as a developmental variant. Studies of prosopagnosia make important contributions to our understanding of face processing and object recognition in the human visual system. We review four areas of advances in the study of this condition in recent years. First are issues surrounding the diagnosis of prosopagnosia, including the development and evaluation of newer tests and proposals for diagnostic criteria, especially for the developmental variant. Second are studies of the structural basis of prosopagnosia, including the application of more advanced neuroimaging techniques in studies of the developmental variant. Third are issues concerning the face specificity of the defect in prosopagnosia, namely whether other object processing is affected to some degree and in particular the status of visual word processing in light of recent predictions from the “many-to-many hypothesis”. Finally, there have been recent rehabilitative trials of perceptual learning applied to larger groups of prosopagnosic subjects that show that face impairments are not immutable in this condition.

Chronic ulcerative stomatitis: A comprehensive review and proposal for diagnostic criteria.

Chronic ulcerative stomatitis (CUS) is an immune-mediated disorder characterized by oral erosions and ulcers usually refractory to conventional treatments. The disease often involves middle-aged and older women with painful lesions sometimes resembling those of erosive oral lichen planus (OLP). The most affected sites are the buccal mucosa, the gingiva and the tongue, but the skin is involved in 22.5% of cases. Histopathologic features in CUS are non-specific and indistinguishable from those of OLP, with the exception of the presence of a mixed infiltrate composed of lymphocytes and plasma cells. Direct immunofluorescence (DIF) analysis reveals the presence of stratified epithelium-specific antinuclear antibodies (SES-ANA) in the lower third of the epithelium. The IgG antibodies detected on DIF are directed against the ∆Np63α isoform of p63 expressed in the nuclei of the epithelial basal cells. A distinguishing feature of CUS is the low response to conventional corticosteroid therapy and the good outcome with hydroxychloroquine at the dosage of 200mg/day or higher dosages. This paper presents a comprehensive review of CUS and is accompanied by a new case report (the 73rd case) and a proposal for updated diagnostic criteria.

300 Gastric Submucosal Lipomatosis Presenting as Gastric Polyposis: The First Case Report and Morphometric Study of Additional 127 Gastric Bypass Specimens With a Proposal for Diagnostic Criteria

300 Gastric Submucosal Lipomatosis Presenting as Gastric Polyposis: The First Case Report and Morphometric Study of Additional 127 Gastric Bypass Specimens With a Proposal for Diagnostic Criteria

LOVA: the role of endoscopic third ventriculostomy and a new proposal for diagnostic criteria

The diagnostic criteria and management of this condition continue to be a topic of debate in the literature. The term definitive symptomatic LOVA (longstanding overt ventriculomegaly in adults) is applied to patients that fulfil a series of diagnostic criteria,which are reviewed in our paper. The main subject of our study is to propose a rearrangement of the criteria for the diagnosis of this entity and adjusted treatment strategies. We present our data evaluating the role of endoscopy in this pathology. This descriptive and analytical study comprised 27 adult patients with LOVA who underwent endoscopic third ventriculostomy (ETV). Data regarding age, gender and onset of symptoms, a previously implanted shunt, clinical examination and radiological findings at the time of diagnosis, and the intracranial pressure (ICP) recordings in some cases, were carefully retrospectively reviewed. ETV success was determined based on clinical state and radiological criteria. ETV was performed in all 27 cases. Mean follow up period was 4.2 years (6 months to 8 years). 2/27 patients (7.40%) were lost to follow-up. The overall success rate for ETV was 76% (21/25 patients). ETV resulted in shunt independency in two of the three patients with a previous shunt. Based on our results, we believe that ETV must be considered as the treatment of choice for patients with symptomatic LOVA.

Post electrical or lightning injury syndrome: a proposal for an American Psychiatric Association's Diagnostic and Statistical Manual formulation with implications for treatment.

In the past, victims of electrical and lightning injuries have been assessed in a manner lacking a systematic formulation, and against ad hoc criteria, particularly in the area of neuropsychological disability. In this manner patients have, for example, only been partially treated, been poorly or incorrectly diagnosed, and have been denied the full benefit of compensation for their injuries. This paper contains a proposal for diagnostic criteria particularly for the neuropsychological aspects of the post injury syndrome. It pays attention to widely published consistent descriptions of the syndrome, and a new cluster analysis of post electrical injury patients. It formulates a proposal which could be incorporated into future editions of the American Psychiatric Association's Diagnostic and Statistical Manual (DSM). The major neuropsychological consequences include neurocognitive dysfunction, and memory subgroup dysfunction, with ongoing consequences, and sometimes including progressive or delayed psychiatric, cognitive, and/or neurological symptoms. The proposed diagnostic criteria insist on a demonstrated context for the injury, both specifying the shock circumstance, and also physical consequences. It allows for a certain delay in onset of symptoms. It recognizes exclusory conditions. The outcome is a proposal for a DSM classification for the post electrical or lightning injury syndrome. This proposal is considered important for grounding patient treatment, and for further treatment trials. Options for treatment in electrical or lightning injury are summarised, and future trials are foreshadowed.

A Proposal of the European Association for the Study of Obesity to Improve the ICD-11 Diagnostic Criteria for Obesity Based on the Three Dimensions Etiology, Degree of Adiposity and Health Risk

Diagnostic criteria for complex medical conditions caused by a multitude of both genetic and environmental factors should be descriptive and avoid any attribution of causality. Furthermore, the wording used to describe a disorder should be evidence-based and avoid stigmatization of the affected individuals. Both terminology and categorizations should be readily comprehensible for healthcare professionals and guide clinical decision making. Uncertainties with respect to diagnostic issues and their implications may be addressed to direct future clinical research. In this context, the European Association of the Study of Obesity (EASO) considers it an important endeavor to review the current ICD-11 Beta Draft for the definition of overweight and obesity and to propose a substantial revision. We aim to provide an overview of the key issues that we deem relevant for the discussion of the diagnostic criteria. We first discuss the current ICD-10 criteria and those proposed in the ICD 11 Beta Draft. We conclude with our own proposal for diagnostic criteria, which we believe will improve the assessment of patients with obesity in a clinically meaningful way.

Michelin tire baby syndrome: a review of the literature and a proposal for diagnostic criteria with adoption of the name circumferential skin folds syndrome.

The term Michelin tire baby (MTB), named for the cartoon mascot of the Michelin Tire Company, has been used to describe babies with multiple symmetric circumferential rings of folded skin. In those reported with this phenotype who had skin biopsies, pathology has shown nevus lipomatosis, smooth muscle hamartoma, degenerative collagen, and scarring. Others did not undergo biopsy or had normal skin. Many individuals with the MTB phenotype have had a variety of other congenital anomalies. I review the literature on MTB and the history of the designation Michelin tire baby Syndrome (MTBS). Because the term MTBS has been poorly defined or not defined at all, I propose strict criteria for diagnosis. In doing so, it is recommended that the syndrome be renamed to avoid further confusion.

Complicated grief – a challenge in bereavement support in palliative care: An update of the field

The philosophy of palliative care recognizes that end-of-life care impacts the whole family. Consequently, palliative care involves support for the family during illness and after the patient's death. Until recently, no clinical guidelines on bereavement support existed in palliative care. Little is known about the extent of bereavement follow-up provided by specialist services. A few surveys show that bereavement programmes may be common, but need to work with best-practice models to ensure optimal allocation of support. An increasing amount of research shows complicated grief as a clinical phenomenon and a distinct diagnostic entity. The fundamental issue is mapping universally valid norms of reactions, including the prevalence of complications, and lately also the pursuit of a diagnostic entity of complicated grief. In the recently released fifth edition of the American Diagnostic and Statistical Manual of Mental Disorders all proposals for diagnostic criteria for complicated grief were rejected. Instead, the committee chose to remove the ‘bereavement exclusion’ of the DSM-IV, which excluded individuals from a diagnosis of major depressive disorder right after a loss. This paper addresses issues related to complicated grief as a bereavement-related disorder, and current implications and challenges in palliative care bereavement support will be discussed. The academic society seems to support a public health framework based on a systematic and evidence-based approach, which builds on needs and risks, to inform the organization of bereavement services. Until a distinctive and clearly defined concept of complicated grief exists and validated assessment tools are applicable, attention to new effective interventions is of vital importance in the provision of bereavement care. Bereavement counsellors in palliative care need to work to provide a clearer platform for evidence-based treatments for complicated grief within the remit of palliative care, or the lack of focus on complicated grief in palliative care is a complicating factor for the bereaved caregivers.

The puzzle of myeloproliferative neoplasms: novel disease-specific mutations and new proposals for diagnostic criteria.

#Hee-Jin Kim and Chul Won Choi contributed equally to this work. Polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are collectively called “Philadelphia-negative classical myeloproliferative neoplasms” (MPNs), and the discovery of the JAK2V617F mutation in 2004 led us to make new progress in the diagnostic approach and therapeutic strategy for MPNs. Thereafter, other clonal markers, such as mutations of the MPL or CALR genes, were discovered and listed as useful markers for the distinction of MPN from reactive myeloproliferation. The identification of recurrent gain-of-function somatic mutations in the JAK2 and MPL genes during the years 2005–2007 provided critical insights into non-BCR/ABL1 MPNs that have advanced our understanding of the molecular pathophysiology of these diseases. The JAK2 and MPL mutations were readily incorporated into the diagnostic criteria for PV, ET, and PMF in the 2008 World Health Organization (WHO) classification [1]. Thereafter, the growing application of high-throughput sequencing technologies to the identification of genetic alterations at the nucleotide level has revealed a long list of genes, other than JAK2 and MPL, which are mutated in MPNs. It is expected that 2 of these genes, CALR and CSF3R, will be added to the upcoming WHO classification, based on their significant frequency of occurrence and genotype-phenotype correlation, particularly in terms of therapeutic and prognostic implications [2]. The CALR gene will appear in the diagnostic criteria for ET and PMF; CALR mutations are reported to be detected in ∼70% of JAK2-nonmutated ET and ∼85% of JAK2-nonmutated PMF. CALR encodes the protein calreticulin, which has multiple functions and plays roles in, for example, cell proliferation and apoptosis. CALR mutations occur exclusively in exon 9 (the last exon) and are most commonly small deletions or insertions, with or without substitutions. The two most common mutations that account for ∼80% of all CALR mutations, c.1092_1143del (p.L367fs*46) and c.1154_1155insTTGTC (p.K385fs*47), have been designated as type 1 and 2, respectively. The mutations both result in a frameshift to an alternative reading frame and generate a novel amino acid sequence at the C-terminus of the protein. Clinically, compared to patients with JAK2 mutations, patients with CALR mutations have a higher platelet count, lower Hb and leukocyte levels, a lower risk of thrombosis, and a more indolent disease course [3]. Interestingly, mutation type was found to be associated with disease subtype (predilection for type 1 mutations in PMF) and with the clinical course of the disease (shorter survival with type 2 mutations in PMF) [4]. Technically, PCR and amplicon-sizing analyses can detect CALR mutations with high sensitivity and provide quantitative information, and direct sequencing analysis can then fully characterize the mutations. Of note, the 3 major driver mutations in non-BCR/ABL1 MPNs, JAK2, MPL, and CALR, occur in an almost mutually

The Diagnosis and Management of Piriformis Syndrome: Myths and Facts

Piriformis Syndrome (PS) is an uncommon, controversial neuromuscular disorder that is presumed to be a compression neuropathy of the sciatic nerve at the level of the piriformis muscle (PM). The diagnosis is hampered by a lack of agreed upon clinical criteria and a lack of definitive investigations such as imaging or electrodiagnostic testing. Treatment has focused on stretching, physical therapies, local injections, including botulinum toxin, and surgical management. This article explores the various sources of controversy surrounding piriformis syndrome including diagnosis, investigation and management. We conclude with a proposal for diagnostic criteria which include signs and symptoms, imaging, and response to therapeutic injections.

Review of Dercum's disease and proposal of diagnostic criteria, diagnostic methods, classification and management.

Definition and clinical pictureWe propose the minimal definition of Dercum’s disease to be generalised overweight or obesity in combination with painful adipose tissue. The associated symptoms in Dercum’s disease include fatty deposits, easy bruisability, sleep disturbances, impaired memory, depression, difficulty concentrating, anxiety, rapid heartbeat, shortness of breath, diabetes, bloating, constipation, fatigue, weakness and joint aches.ClassificationWe suggest that Dercum’s disease is classified into: I. Generalised diffuse form A form with diffusely widespread painful adipose tissue without clear lipomas, II. Generalised nodular form - a form with general pain in adipose tissue and intense pain in and around multiple lipomas, and III. Localised nodular form - a form with pain in and around multiple lipomas IV. Juxtaarticular form - a form with solitary deposits of excess fat for example at the medial aspect of the knee.EpidemiologyDercum’s disease most commonly appears between the ages of 35 and 50 years and is five to thirty times more common in women than in men. The prevalence of Dercum’s disease has not yet been exactly established.AetiologyProposed, but unconfirmed aetiologies include: nervous system dysfunction, mechanical pressure on nerves, adipose tissue dysfunction and trauma.Diagnosis and diagnostic methodsDiagnosis is based on clinical criteria and should be made by systematic physical examination and thorough exclusion of differential diagnoses. Advisably, the diagnosis should be made by a physician with a broad experience of patients with painful conditions and knowledge of family medicine, internal medicine or pain management. The diagnosis should only be made when the differential diagnoses have been excluded.Differential diagnosisDifferential diagnoses include: fibromyalgia, lipoedema, panniculitis, endocrine disorders, primary psychiatric disorders, multiple symmetric lipomatosis, familial multiple lipomatosis, and adipose tissue tumours.Genetic counsellingThe majority of the cases of Dercum’s disease occur sporadically. A to G mutation at position A8344 of mitochondrial DNA cannot be detected in patients with Dercum’s disease. HLA (human leukocyte antigen) typing has not revealed any correlation between typical antigens and the presence of the condition.Management and treatmentThe following treatments have lead to some pain reduction in patients with Dercum’s disease: Liposuction, analgesics, lidocaine, methotrexate and infliximab, interferon α-2b, corticosteroids, calcium-channel modulators and rapid cycling hypobaric pressure. As none of the treatments have led to long lasting complete pain reduction and revolutionary results, we propose that Dercum’s disease should be treated in multidisciplinary teams specialised in chronic pain.PrognosisThe pain in Dercum’s disease seems to be relatively constant over time.

IgG4-related meningeal disease: clinico-pathological features and proposal for diagnostic criteria

IgG4-related disease has evolved from originally being recognized as a form of pancreatitis to encompass diseases of numerous organs including the hypophysis and one reported case of dural involvement. A search of the University of Virginia, Division of Neuropathology files for 10 years identified ten cases of unexplained lymphoplasmacytic meningeal inflammation that we then evaluated using immunohistochemical stains for IgG4 and IgG. Ten control cases including sarcoidosis (4), tuberculosis (1), bacterial abscess (2), Langerhans cell histiocytosis (2), and foreign body reaction (1) were also examined. The number of IgG4-positive plasma cells was counted in five high power fields (HPFs) and an average per HPF was calculated. Cases that contained greater than ten IgG4-positive cells/HPF were considered to be IgG4-related. Five of the study cases met these criteria, including one case of leptomeningeal inflammation. All cases exhibited the typical histological features of IgG4-related disease including lymphoplasmacytic inflammation, fibrosis, and phlebitis. The dural-based lesions appear to represent a subset of the cases historically diagnosed as idiopathic hypertrophic pachymeningitis. While the leptomeningeal process most closely resembles non-vasculitic autoimmune inflammatory meningoencephalitis. Given these findings, IgG4-related meningitis should be considered in the differential diagnosis of meningeal inflammatory lesions after stringent clinical and histologic criteria are used to rule out other possible diagnoses.

Serrated polyps of the colon and rectum (hyperplastic polyps, sessile serrated adenomas, traditional serrated adenomas, and mixed polyps)—proposal for diagnostic criteria

Until recently, two major types of colorectal epithelial polyps were distinguished: the adenoma and the hyperplastic polyp. While adenomas-because of their cytological atypia-were recognized as the precursor lesions for colorectal carcinoma, hyperplastic polyps were perceived as harmless lesions without any potential for malignant progression mainly because hyperplastic polyps are missing cytological atypia. Meanwhile, it is recognized that the lesions, formerly classified as hyperplastic, represent a heterogeneous group of polyps with characteristic serrated morphology some of which exhibit a significant risk of neoplastic progression. These serrated lesions show characteristic epigenetic alterations not commonly seen in colorectal adenomas and progress to colorectal carcinoma via the so-called serrated pathway (CpG-island-methylation-phenotype pathway). This group of polyps is comprised not only of hyperplastic polyps, but also of sessile serrated adenomas, traditional serrated adenomas and mixed polyps, showing serrated and "classical" adenomatous features. Diagnostic criteria and nomenclature for these lesions are not uniform and, therefore, somewhat confusing. In a consensus conference of the Working Group of Gastroenterological Pathology of the German Society of Pathology, standardization of nomenclature and diagnostic criteria as well as recommendations for clinical management of these serrated polyps were formulated and are presented herein.

Cutis marmorata telangiectatica congenita: a prospective study of 27 cases and review of the literature with proposal of diagnostic criteria

Cutis marmorata telangiectatica congenita (CMTC) is a congenital vascular anomaly of unknown aetiology. About 300 cases have been reported in the literature. The rate of associated anomalies varies between 20% and 70%. We report a series of 27 children with CMTC, 18 of whom were followed-up prospectively for a median of 22 months (range 2 months-5.3 years). Both genders were equally affected (13 male/14 female). The legs were involved in 20 cases (74%), the arms in 10 (37%), the face in 4 (15%) and the trunk in 18 (67%). There were 20 (74%) patients who presented with involvement of both trunk and limbs, a further 20 patients had lesions affecting the limb on only one side of the body, and 7 children (26%) had bilateral lesions; 1 child had generalized CMTC lesions. The involved areas covered a mean of 18% of body surface area (range 3-90). Associated anomalies were found in 15 patients (56%), with some exhibiting more than one. There was body asymmetry (hypertropy or hypotrophy of the affected limb) in nine patients (33%), seven patients had a variety of other malformations (congenital glaucoma, syndactyly, lipoma, macrocephaly, renal hypoplasia, Kartagener's syndrome), and other vascular lesions were present in four patients (15%). There was no correlation between the extent of skin lesions and likelihood of associated anomalies. On follow-up, fading of skin lesions was noted in 67% of our patients. Body asymmetry is the most common anomaly associated with CMTC; other associations might be pure chance. In order to separate CMTC from other vascular malformations, notably Klippel-Trénaunay syndrome, we suggest diagnostic criteria for their differentiation.

Clinical usefulness of measurement of fibroblast growth factor 23 (FGF23) in hypophosphatemic patients: Proposal of diagnostic criteria using FGF23 measurement

Fibroblast growth factor 23 (FGF23) plays important roles in the development of hypophosphatemic diseases such as tumor-induced osteomalacia (TIO) and X-linked hypophosphatemic rickets/osteomalacia (XLH). However, clinical usefulness of measurement of FGF23 has not been established. The objective of this study is to examine the importance of FGF23 measurement in the diagnosis of hypophosphatemic diseases. Biochemical parameters concerning phosphate metabolism were analyzed in a cross-sectional study. 32 patients with TIO, 28 patients with XLH and 16 hypophosphatemic patients with other causes including vitamin D deficiency, Fanconi's syndrome and Cushing's syndrome were studied. In patients with TIO and XLH, FGF23 was above the upper limit of the reference range in most patients irrespective of medical treatment. The lowest FGF23 in these patients was 38.0 pg/ml. FGF23 in hypophosphatemic patients with other causes was undetectable (less than 3 pg/ml) in 12 patients and the highest FGF23 in this group was 23.9 pg/ml. Relationship between phosphate and FGF23 indicated that TIO and XLH are diseases with high FGF23 and hypophosphatemia judged by age-dependent reference ranges for serum phosphate. FGF23 measurement is useful for differential diagnosis of hypophosphatemic diseases caused by excess actions of FGF23 and other etiologies. High FGF23 with low phosphate judged by age-dependent reference ranges for phosphate establishes the diagnosis of diseases caused by excess actions of FGF23.