Additional Clinical Signs Research Articles

Clinical-Instrumental patterns of neurodegeneration in Essential Tremor: A data-driven approach

IntroductionEssential Tremor (ET) is increasingly recognized as a complex disorder with additional clinical signs other than tremor. It is still unknown whether a unique pathophysiologic or neurodegenerative process underlies progression and prognosis of the disease. The aim of the study was to identify ET phenotypes through a clinical-instrumental data-driven approach and to characterize possible patterns of neurodegeneration. MethodsET patients were categorized using spatio-temporal and kinematic variables related to mobility and dynamic stability processed by motion transducers. Differences between the identified groups in clinical-demographic variables, neuropsychological performances and retinal parameters by Optical Coherence Tomography (OCT) segmentation analysis were tested. ResultsTwenty-five ET patients were studied. Based on clustering of kinematic and spatio-temporal gait parameters, two independent groups were identified: cluster “A” (N = 15) and cluster “B” (N = 10). Compared to group A, group B had overall worse performance in mobility, especially on turning tasks. Identified clusters did not differ in terms of age, age at onset and disease duration. Patients in group B had more head tremor and more severe action tremor in the upper limbs as compared to group A, demonstrating also worse performances on cognitive assessments. Based on OCT analysis, group B presented a reduced thickness of the retinal inner layer as compared to group A, suggesting underlying neurodegenerative processes. ConclusionsThe presence of gait and mobility impairment, associated with midline tremor, cognitive decline and retinal degeneration suggests a subtype of ET associated with neurodegeneration.

Cerebrotendinous xanthomatosis without neurological involvement.

Cerebrotendinous xanthomatosis (CTX) is an autosomal recessively inherited inborn error of metabolism. Neurological symptoms are considered to be a clinical hallmark of untreated adult patients. We describe a 'milder CTX phenotype', without neurological involvement. We performed a retrospective patient file study in 79 genetically confirmed Dutch patients with CTX (55 patients aged≥21years) to study the clinical heterogeneity of CTX. We studied the frequency of adult patients with CTX without neurological involvement at diagnosis, in our Dutch cohort, and included a family from South Africa and patients from Italy, USA, Chile and Asia from the literature. In total, we describe 19 adult patients with CTX from 16 independent families, without neurological symptoms at diagnosis. A relatively small percentage (21%, n=4) had a history of cataract. The majority, 84% (n=16), presented with tendon xanthomas as the sole or predominant feature. The majority of patients showed increased plasma cholesterol levels. No correlation was found between this 'milder phenotype', the cholestanol levels and the CYP27A1 genotype. In addition, we describe three novel mutations in the CYP27A1 gene. This study shows the clinical heterogeneity of CTX, highlighting the existence of a 'milder phenotype', that is without neurological involvement at diagnosis. Adult patients with CTX may present with tendon xanthomas as the sole or predominant feature, mimicking familial hypercholesterolemia. It is important to realize that the absence of neurological symptoms does not rule out the development of future neurological symptoms. As CTX is a treatable disorder, early diagnosis and initiation of treatment when additional clinical signs occur is therefore essential.

Bovine congenital babesiosis

Diagnostic Exercise from The Latin Comparative Pathology Group. Clinical History: A crossbred, stillborn bovine fetus, with nine months of gestation, was submitted for postmortem examination. The dam that aborted was a 2-year-old heifer that did not have any additional clinical signs. The owner observed several late-term abortions and stillbirths in this farm during the referred calving season. Necropsy Findings: Necropsy findings included moderate accumulation of light red fluid in the abdominal and thoracic cavities, mild hemoglobin imbibition, as well as collapsed lungs. The liver was markedly enlarged, had rounded edges, and moderate, diffuse yellow discoloration. The gallbladder was filled with thick, grumous bile, and the spleen was moderately enlarged. The kidneys had moderate diffuse dark red discoloration, and the urinary bladder was distended with dark-red urine. The grey matter of the brain and the spinal cord was markedly pink-red discolored. Squashes of the spleenand brain were prepared and routinely stained with PanóticoRápido® (Laborclin, Brazil).

Equine Sialolithiasis of the Distal Parotid Duct. Retrospective Study on 4 Cases

Sialolithiasis is an infrequently encountered condition in equids, although it occurs more frequently in equine species than other domestic species. Sialoliths appear smooth or slightly spiculated, and gray, yellowish, or white. The most common presentation is within the parotid duct, usually at its most rostral portion, just before it opens into the vestibule opposite the third upper cheek tooth with very few cases affecting the mandibular duct. Typically, a non-painful, movable, firm structure is palpable on the lateral aspect of the face near the rostral end of the facial crest, and it can be present for many years before additional clinical signs develop and lead to veterinary attention. In total, three horses and one donkey (four equines) were included in this study. All animals were in good clinical condition. None of these cases showed signs of concurrent sialadenitis or had problems eating. A detailed teeth examination showed severe enamel overgrowths on all arcades. In all cases, diagnosis of sialolithiasis was based on clinical presentation and palpation and was confirmed by surgically removing the sialolith. All sialoliths were removed with the animals standing under sedation and local anesthesia. In one case, a decision was made to remove the sialolith through a transcutaneous approach with ligation of the parotid duct at its rostral end. For the remaining three cases the transoral technique was elected. Although the size of the removed sialoliths varied, they ranged from 6 to 8cm in length. All four sialoliths were dissected, with no evidence of a plant or any other foreign material found in any of them. The first horse, in which the transcutaneous excision was elected, developed a marked distention of the parotid duct. Although the incision wound closed nicely, a visible blemish was created because of the retrograde distention of the parotid duct. In the remaining three animals, which were operated via the transoral technique, improvement was immediately seen following surgery and no blemishes or any other complications were noted. On patient follow-up via telephone 3 years post-operatively, no signs of sialolith re-growth were noted by the owners. Based on the results of this study, it is recommended that sialoliths should be identified as early as possible at the course of the disease, before they grow substantially in size, and that the transoral surgical excision is the treatment of choice provided that the sialolith is accessible orally.

Polyneuropathy in POEMS Syndrome

A rare version of paraproteinemic hemablastosis, with the onset characterized by Peripheral Nerve Disease, is POEMS- syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin Changes). In the foreground of the clinical picture of this oncohematological disease is progressive sensorimotor polyneuropathy, which is the reason for the primary reference to a neurologist long before the provision of specialized hematological care. The article provides an overview of recent scientific publications devoted to this disease. Its pathogenetic mechanisms are discussed, as well as the basis of endothelial growth factor. The authors present their own clinical observation of a 62-year-old patient. The onset of the disease was characterized by polyneuropathy accompanied by changes in the M-protein index, organomegaly in the absence of bone-destructive changes, which made the diagnosis difficult. Additional clinical signs included fever, edema (ascites, exudative pleurisy), and hypoproteinemia, changes in peripheral blood (moderate leukocytosis with a decrease in the level of erythrocytes and platelets, which is atypical), kidney and cardiovascular damage. Despite the specific therapy, the patient’s condition was complicated by the development of infectious complications and was fatal. This clinical observation illustrates the need for a careful differential search for a possible cause of non-polyneuropathy of unknown genesis.

Multisystemic manifestations in a cohort of 75 classical Ehlers-Danlos syndrome patients: natural history and nosological perspectives

BackgroundThe Ehlers-Danlos syndromes (EDS) are rare connective tissue disorders consisting of 13 subtypes with overlapping features including joint hypermobility, skin and generalized connective tissue fragility. Classical EDS (cEDS) is principally caused by heterozygous COL5A1 or COL5A2 variants and rarely by the COL1A1 p.(Arg312Cys) substitution. Current major criteria are (1) skin hyperextensibility plus atrophic scars and (2) generalized joint hypermobility (gJHM). Minor criteria include additional mucocutaneous signs, epicanthal folds, gJHM complications, and an affected first-degree relative. Minimal criteria prompting molecular testing are major criterion 1 plus either major criterion 2 or 3 minor criteria. In addition to these features, the clinical picture also involves multiple organ systems, but large-scale cohort studies are still missing. This study aimed to investigate the multisystemic involvement and natural history of cEDS through a cross-sectional study on a cohort of 75 molecularly confirmed patients evaluated from 2010 to 2019 in a tertiary referral center. The diagnostic criteria, additional mucocutaneous, osteoarticular, musculoskeletal, cardiovascular, gastrointestinal, uro-gynecological, neuropsychiatric, and atopic issues, and facial/ocular features were ascertained, and feature rates compared by sex and age.ResultsOur study confirms that cEDS is mainly characterized by cutaneous and articular involvement, though none of their hallmarks was represented in all cases and suggests a milder multisystemic involvement and a more favorable natural history compared to other EDS subtypes. Abnormal scarring was the most frequent and characteristic sign, skin hyperextensibility and gJHM were less common, all without any sex and age bias; joint instability complications were more recurrent in adults. Some orthopedic features showed a high prevalence, whereas the other issues related to the investigated organ systems were less recurrent with few exceptions and age-related differences.ConclusionsOur findings define the diagnostic relevance of cutaneous and articular features and additional clinical signs associated to cEDS. Furthermore, our data suggest an update of the current EDS nosology concerning scarring that should be considered separately from skin hyperextensibility and that the clinical diagnosis of cEDS may be enhanced by the accurate evaluation of orthopedic manifestations at all ages, faciocutaneous indicators in children, and some acquired traits related to joint instability complications, premature skin aging, and patterning of abnormal scarring in older individuals.

SAT-263 A Vicious Cycle of Hypercortisolism - Cyclical Cushing’s Syndrome

Background: Cyclical Cushing’s syndrome (CS) is described as periods of excess cortisol secretion interspersed with low or normal cortisol. The generally acceptable criteria for diagnosis is demonstration of 3 peaks and 2 troughs in cortisol secretion but, in practice, patterns and duration of cycles are unpredictable and can present a significant diagnostic challenge. Here, we present a case series of three patients who did not meet the published criteria but had pathological confirmation of ACTH-dependent CS. Clinical Case: Two women (A: 30 year-old, B: 40 year-old), and one man (C: 30 year-old) presented to the Pituitary Center for second/third opinions regarding CS. All patients had significant central weight gain. Patient A described cycles of rapid weight gain and loss, fluctuating facial and leg swelling, anxiety and darkening of stretch marks or scars punctuated with episodes of fatigue, lightheadedness and nausea. Patients B and C reported cyclical leg swelling, facial redness and acne. These patients had additional clinical signs of Cushingoid facies, dorsocervical and supraclavicular fat pads. Patient C had violaceous striae.Multiple tests for CS were performed: 1 mg overnight dexamethasone suppression test, two midnight salivary cortisols, and 24h urine free cortisol (UFC). All testing was normal, with a few exceptions. Patient A had an isolated midnight salivary cortisol elevated to 0.426 (<0.112 ug/dL). Patient C had two mildly elevated 24h UFC collections of 1.4 times upper limit of normal corresponding with his cycles of peripheral edema and acne. Patient B had completely negative testing. In all 3 patients, ACTH levels were not suppressed but also not elevated. Random serum DHEA-S levels were elevated in patients A and B.Patients A and C were found to have possible pituitary microadenomas on MRI with dynamic contrast. Patient B’s MRI was negative but inferior petrosal sinus sampling revealed a markedly elevated tumoral level of ACTH of >62,500 pg/mL with CRH stimulation. All 3 patients underwent endoscopic transsphenoidal resection by an expert pituitary surgeon with no post-operative complications in patients A & B, but development of partial diabetes insipidus in patient C. In patients A & C, pathology revealed corticotroph hyperplasia while patient B was found to have a corticotroph adenoma. Patients A & B persisted to have symptoms of hypercortisolism, opted to undergo bilateral adrenalectomy and pathology showed diffuse adrenocortical hyperplasia for both. Conclusion: Cyclical CS is likely underdiagnosed because of difficulty in obtaining biochemical confirmation even with strong clinical suspicion of CS. DHEA-S has a long half-life as well as minimal diurnal variation, and could be an additional clue in patients with suspected pituitary source of cyclical hypercortisolism. Ultimately, clinical concern should drive further diagnostic imaging and management.

From the Literature

From the Literature

Übersicht zu Zusammenhängen zwischen Änderungen der Bewegungsintensität und Ketose bei Milchkühen

With a prevalence of up to 43 % subclinical ketosis is one of the most common diseases in dairy cows in their transition period. In itself, this may cause subsequent diseases such as clinical ketosis or lameness. Therefore, monitoring of animals in this stage is of importance. In addition to the measurement of β-hydroxybutyrate or acetoacetate in blood, milk, and urine as well as the observation of the animals, computer-assisted systems are suitable means of monitoring. Information such as animal identification and activity data are recorded on a data logger and transmitted to a computer. A change in activity may be an indication of an underlying disease days before the onset of additional clinical signs. In cases of ketosis, a decrease in activity may be observed 5 days before the clinical diagnosis is made. Thus, these data are a valuable contribution in monitoring the cattle herd's health status for both the farmer and the veterinarian. Activity measurement may also be employed for the detection of a beginning lameness. In the presence of lameness, the individual's activity decreases and periods of lying are longer. Activity measurement via transponder as a part of the herd monitoring provides important information on lameness prevalence in the herd. In the presence of a lameness a visual assessment should additionally be made. Lameness scores (Locomotion score, Gait score) have been developed for this purpose and add to determining the lameness status of the herd. This way the animals are divided into different lameness classes. Based on this classification those individuals in need of claw trimming or further treatment may be identified leading to amelioration or prevention of secondary diseases. Due to lameness and subsequent reduction of activity and feed intake, the animals may develop subclinical or clinical ketosis. Therefore, under consideration of both animal welfare and economic factors early disease detection and prophylaxis is desirable and should be a main objective of herd monitoring.

Clinical presentation of FMD virus SAT1 infections in experimentally challenged indigenous South African goats

Abstract Foot-and-mouth disease (FMD) is a transboundary animal disease that has a major impact on livestock production and trade. Foot-and-mouth disease virus (FMDV) is a single-stranded RNA virus that infects cloven-hoofed livestock and wildlife. The susceptibility of South African indigenous goats to FMDV Southern African Territories 1 (SAT1) was investigated after experimental challenge with a mixed SAT1 virus pool. In this study, we present the clinical manifestation of FMDV in five naive goats challenged via the intra-dermolingual route with 104.57 50% tissue culture infective dose (TCID50) FMDV virus pool containing SAT1 SAR/8/10, SAR/10/10 and SAR/21/10. The clinical responses of two vaccinated unchallenged goats maintained as in-contacts are also presented. Clinical scoring of FMDV infection and daily rectal temperatures were recorded and temperatures ≥40 °C were defined as fever. All five challenged goats developed fever within 48 h post challenge with a median fever duration of 5 days. The two unchallenged goats developed fever at 5 and 9 days post-contact with FMD lesions appearing at 4 and 8 days post-contact. Additional clinical signs observed included nasal discharge, ulcerative oral mucosal lesions of the lip and ulcerative interdigital cleft lesions. The pooled FMDV SAT1 infection caused mild clinical signs and natural transmission to reduced-dose vaccinated in-contact indigenous South African goats occurred.

The expression of Interlukin 2(IL-2), Interlukin 8(IL-8) and Interlukin 6(IL-6) in patients with oral and oropharyngeal squamous cell carcinoma in Basrah city (A case control study)

The first part of the digestive tract is the oral mucosa, which exposed to different exogenous toxins, long period of exposure could lead to malignant changes/tumors. One of the prevalent cancers of the body is Oral squamous cell carcinoma, oral cancer sometimes may be resemble benign lesions in the mouth therefor, the diagnosis may be not easy clinically. There appear the importance of serum cytokines in distinguishing different pathologies.Aims: The aim of this study was to identify the role of serum Interlukins (IL2, IL6, IL8) in the early detection and pathogenesis of oral and oropharyngeal squamous cell carcinoma. Patients and Methods: This study included 20 patients with oral and oropharyngeal squamous cell carcinoma were clinically diagnosed and then confirmed by histopathological examination and 26 healthy control. Age, gender, as well as the level of interlukins in the serum of patients and healthy control were measured, in addition clinical signs and the site of lesions were recorded for patients group. Results: There were 20 new cases of oral and oropharyngeal squamous cell carcinoma in Basrah from September 2015 to December 2016, 12 in men and 8 in women. 26 healthy control individuals 17 men and 9 female were included in this study. Cancer at all oral sites affected men more than women. The Tongue is the most frequent site. The level of serum Interlukins (IL2, IL6, IL8) in patients group were much more than those in healthy control group.

Leptospirosis: An important infectious disease in North American horses.

North American horses are commonly exposed to Leptospira organisms. Leptospira Bratislava is the most common infecting serovar but this serovar has not been confirmed to cause clinical disease in North American horses. Leptospira Pomona type kennewicki is responsible for most of the clinical diseases (leptospirosis) in North American horses. Leptospirosis is most commonly associated with diseases of the placenta and fetus, the kidneys and the eyes in horses. In-utero infections in pregnant mares may result in abortion, neonatal illness or birth of an antibody positive healthy foal. Acute renal failure in younger horses and recurrent uveitis in adult horses are other well documented clinical syndromes of leptospirosis. Abortions, neonatal disease and acute renal failure are caused by a subacute infection, while horses with Leptospira associated recurrent uveitis develop ocular disease months or years after the initial Leptospira infection. Diagnosis of Leptospirosis is made by a combination of antigen or antibody testing methods. Mares that abort following Leptospira infection have no additional clinical signs at the time of abortion but may shed the offending Leptospira spp. in the urine for several weeks. Antibiotic treatments are sometimes used in hopes of decreasing Leptospira shedding in infected horses or prophylactically in exposed pregnant mares but documentation of efficacy is lacking. Horses with Leptospira - associated acute renal failure can be successfully treated with antibiotics and supportive care. Recurrent uveitis is commonly associated with leptospirosis in North American horses and although horses may have chronic intraocular infection triggering an immune disease, systemic antimicrobial therapy has not been effective in eliminating the organism from the eye. An equine approved Leptospira Pomona type kennewicki vaccine is now available in North America.

Body weight changes and incidence of cachexia after stroke.

BackgroundBody weight loss is a frequent complication after stroke, and its adverse effect on clinical outcome has been shown in several clinical trials. The purpose of this prospective longitudinal single‐centre observational study was to investigate dynamical changes of body composition and body weight after ischemic stroke and an association with functional outcome.MethodsSixty‐seven consecutive patients (age 69 ± 11 years, body mass index 27.0 ± 4.1 kg/m2, 42% female patient, mean ± SD) with acute ischemic stroke with mild to moderate neurological deficit (National Institute of Health Stroke Scale median 4, ranged 0–12) were analysed in the acute phase (4 ± 2 days) and at 12 months (389 ± 26 days) follow‐up. Body composition was examined by dual energy X‐ray absorptiometry. Cachexia was defined according to the consensus definition by body weight loss ≥5% within 1 year and additional clinical signs. Lean tissue wasting was considered if a ratio of upper and lower limbs lean mass sum to squared height (kg/m2) was ≤5.45 kg/m2 for female patient and ≤7.25 kg/m2 for male patient.ResultsAccording to the body weight changes after 12 months, 42 (63%) patients had weight gain or stable weight, 11 (16%) patients had moderate weight loss, and 14 (21%) patients became cachectic. A relative decline of 19% of fat tissue and 6.5% of lean tissue was observed in cachectic patients, while no changes of lean tissue were observed in non‐cachectic patients after 12 months. The modified Rankin Scale was 48% higher (2.1 ± 1.6, P < 0.05), Barthel Index was 22% lower (71 ± 39, P < 0.01), and handgrip strength was 34% lower (21.9 ± 13.0, P < 0.05) in cachectic compared to non‐cachectic patients after 12 months.The low physical performance if defined by Barthel Index <60 points was linked to the lean tissue wasting (OR 44.8, P < 0.01), presence of cachexia (OR 20.8, P < 0.01), and low body mass index <25 kg/m2 (OR 11.5, P < 0.05). After adjustment for cofounders, lean tissue wasting remained independently associated with the low physical performance at 12 months follow‐up (OR 137.9, P < 0.05).ConclusionsIn this cohort study, every fifth patient with ischemic stroke fulfilled the criteria of cachexia within 12 months after index event. The incidence of cachexia was 21%. Cachectic patients showed the lowest functional and physical capacity.

A HS6ST2 gene variant associated with X-linked intellectual disability and severe myopia in two male twins.

X‐linked intellectual disability (XLID) refers to a clinically and genetically heterogeneous neurodevelopmental disorder, in which males are more heavily affected than females. Among the syndromic forms of XLID, identified by additional clinical signs as part of the disease spectrum, the association between XLID and severe myopia has been poorly characterized. We used whole exome sequencing (WES) to study two Italian male twins presenting impaired intellectual function and adaptive behavior, in association with severe myopia and mild facial dysmorphisms. WES analysis detected the novel, maternally inherited, mutation c.916G > C (G306R) in the X‐linked heparan sulfate 6‐O‐sulfotransferase 2 (HS6ST2) gene. HS6ST2 transfers sulfate from adenosine 3′‐phosphate, 5′‐phosphosulfate to the sixth position of the N‐sulphoglucosamine residue in heparan sulfate (HS) proteoglycans. Low HS sulfation levels are associated with defective optic disc and stalk morphogenesis during mammalian visual system development. The c.916G>C variant affects the HS6ST2 substrate binding site, and its effect was considered “deleterious” by in‐silico tools. An in‐vitro enzymatic assay showed that the HS6ST2 mutant isoform had significantly reduced sulphotransferase activity. Taken together, the results suggest that mutant HS6ST2 is possibly involved in the development of myopia and cognitive impairment, characteristics of the probands reported here.

Clinical response to isotretinoin and interferon-\u03b1 of two dogs with cutaneous epitheliotropic T-cell lymphoma: a case report

BackgroundThere is no specific therapy for cutaneous epitheliotropic T-cell lymphoma (CETL). The administration of retinoids in conjunction with interferon-α (IFN-α) in CETL has not been reported in dogs.Case presentationTwo dogs (Shih tzu and Miniature pinscher) presented with multiple nodular skin lesions. Histopathological examination revealed diffuse infiltrations of lymphocytes in the epidermis and dermis, with a CD3-positive immunophenotypic profile. Based on the clinical and histopathological examination, CETL was diagnosed. Both dogs were treated with isotretinoin in combination with IFN-α and showed clinical improvement with complete or partial remission. The disease in these dogs was well-controlled for more than 264 days of overall median survival time without any additional clinical signs after initiation of the treatment. In both the cases, the dogs were followed up for 27 months, and 10 months without any evidence of recurrence or metastasis, respectively.ConclusionsWe describe the clinical efficacy of isotretinoin combined with IFN-α in 2 dogs with CETL. Long-term management with isotretinoin combined with IFN-α was effective in treating CETL in these cases.

Tongue Atrophy in Sjögren Syndrome Patients with Mucosa-associated Lymphoid Tissue Lymphoma: Autoimmune Epithelitis beyond the Epithelial Cells of Salivary Glands?

Primary Sjögren syndrome (pSS), an autoimmune epithelitis, bears the risk of evolving to non-Hodgkin lymphoma and most frequently to the mucosa-associated lymphoid tissue (MALT) subtype. Based on the observation that pSS patients with MALT present a more atrophic and more intensely fissured tongue, we aimed to semiquantify severity of tongue atrophy and clinically assess lingual appearance in pSS patients with and without MALT, and investigate whether tongue atrophy and fissured appearance could serve as clinical indicators/signs of MALT. A blinded complete oral examination was performed in pSS patients with and without MALT. Tongue atrophy was scored using a semiquantified atrophy score. Clinical and laboratory variables were recorded for all patients. After excluding pSS patients with oral candidiasis, iron deficiency, and megaloblastic anemia, 19 pSS patients with salivary MALT were matched 1:3 for age, sex, and disease duration with 57 pSS patients without MALT. The pSS-MALT patients had increased prevalence of salivary gland enlargement, lymphadenopathy, monoclonal gammopathy, rheumatoid factor positivity, higher focus and Tarpley scores in the minor salivary gland biopsy, and hyposalivation, compared to the pSS non-MALT patients. A significantly higher prevalence of tongue atrophy (68% vs 30%, p = 0.006) and fissured tongue (89% vs 33%, p < 0.001) was observed in the former group. Multivariate analysis showed that fissured tongue appearance, hyposalivation, and lymphadenopathy associate independently with salivary MALT in pSS. These results suggest that pSS patients with lymphoid malignancy exhibit a more atrophic and more fissured tongue. This particular clinical tongue appearance can serve as an additional clinical sign for salivary MALT lymphoma in pSS patients.

Common symptoms for a rare disease in a girl with sarcoidosis: a case report

BackgroundSarcoidosis in pediatric age is uncommon and challenging diagnosis, because manifestations can be significantly variable and non-specific since it is a multisystem disease, and virtually any organ system may be involved.Case presentationIn this report, we describe the case of a 12-year-old girl presenting with fatigue and weight loss, with a painless hepato-splenomegaly without additional clinical signs on physical examination. In our patient, once we had ruled out infections, malignancies and granulomatous diseases of childhood, we made diagnosis of sarcoidosis, finding suggestive histological features in two different tissues (liver and lymph nodes) with lung involvement.ConclusionsOur case points out that pediatricians should consider sarcoidosis in the differential diagnosis in case of systemic symptoms, even in absence of other specific clinical clues, because they represent the most common clinical manifestations on presentation in children, in order to refer promptly the young patient to specialist evaluation.

Emphysematous and Granulomatous Submucosal Rumenitis in a Feedlot Nellore Steer.

Background: Emphysematous rumenitis is a condition characterized by gas filled bubbles or cysts in the ruminal mucosa. Although a similar pathology is reported from swine and humans, the incidence of this disease in cattle seems to be scarce. The etiology of emphysematous rumenitis is uncertain once many factors can be involved in its pathogeny, a single cause is difficult to ascertain. This lesion usually fails to display specific clinical signs; however, some degree of malabsorption and weight loss is expected. We described a case of emphysematous granulomatous submucosal rumenitis in a 2.5-yearold feedlot Nellore steer that presented reduction on daily weight gain.Case: Rumen fragments of a 2.5-year-old Nellore steer were submitted for histopathological evaluation at the Sector of Pathological Anatomy (SAP) of the Rural Federal University of Rio de Janeiro, Brazil. The specimens were part of an experimental trial to evaluate the effect of phosphorus (P) supplementation on nutrient intake, performance and P balance in fifty feedlot Nellore steers. Following a short adaptation period, in which behavioral observations were made twice daily to assess possible adverse factors, all steers were fed with balanced diet for one hundred and sixteen days. The steers were then slaughtered in order to evaluate macroscopic changes in the gastrointestinal system. Rumen and abomasum of each steer was emptied, washed with tap water and grossly examined. One steer presented ruminal lesion, while the other forty-nine did not show any ruminal injury. Throughout the experiment the affected steer showed reduction of daily weight gain; but during clinical examination no additional clinical sign was seen. At gross inspection, a reduction in the amount of muscular and adipose tissue was seen. Multiple coalescent bullous elevated structures measuring three to ten mm diameter were covering about 40% of the ruminal surface. The affected ruminal mucosa showed irregular and atrophic papillae. Rumen samples were processed routinely and stained with Hematoxylin and Eosin, Period Acid Schiff (PAS), Grocott’s Methenamine Silver (GMS), Ziehl-Neelsen (ZN), Brown-Hopps (Gram), Giemsa and Toluidine Blue (TB) stains. Additionally formalin-fixed, paraffin wax-embedded sections were stained with a primary polyclonal rabbit antibody for Escherichia coli. Histologically the submucosa was largely replaced by cyst-like enlarged lymphatic vessels filled with gaseous content and the ruminal submucosa was infiltrated by macrophages, multinucleated giant cells, eosinophils, lymphocytes and plasma cells. Special stains were negative for granules within the mast cells, fungi, acid-fast bacilli, bacteria and protozoa. E. coli was immuno-labeled only at the ruminal epithelial surface.Discussion: This paper provided a description of a rare and possible underdiagnosed condition in cattle to highlight the necessity of recognizing ruminal changes during slaughterhouse inspection. The spontaneous and extensive emphysematous rumenitis described in this paper showed histological similarities with the analogous condition documented in the small and large intestine, mesentery and mesenteric lymph node of swine. The etiology and pathogenesis of emphysematous submucosal rumenitis remain unknown. We believe that the lesion described was the reason for the decrease of weight gain of the steer; therefore it should be considered as a differential diagnosis for conditions that affect weight gain and performance of cattle.Keywords: cattle, veterinary pathology, feedlot, emphysema, rumen.

The positive predictive value of asymmetrical skin creases in the diagnosis of pathological developmental dysplasia of the hip.

The aim of this study was to identify the association between asymmetrical skin creases of the thigh, buttock or inguinal region and pathological developmental dysplasia of the hip (DDH). Between 1 January 1996 and 31 December 2016, all patients referred to our unit from primary or secondary care with risk factors for DDH were assessed in a "one stop" clinic. All had clinical and sonographic assessment by the senior author (RWP) with the results being recorded prospectively. The inclusion criteria for this study were babies and children referred with asymmetrical skin creases. Those with a neurological cause of DDH were excluded. The positive predictive value (PPV) for pathological DDH was calculated. A total of 105 patients met the inclusion criteria. There were 71 girls and 34 boys. Only two were found to have pathological DDH. Both also had unilateral limited abduction of the hip in flexion and a positive Galeazzi sign with apparent leg-length discrepancy. Thus, if the specialist examination of a patient with asymmetrical skin creases was normal, the PPV for DDH was 0%. Isolated asymmetrical skin creases are an unreliable clinical sign in the diagnosis of pathological DDH. Greater emphasis should be placed on the presence of additional clinical signs to guide radiological screening in babies and children. Cite this article: Bone Joint J 2018;100-B:675-9.

THE FEATURES OE CLINICAL AND LABORATORY DIAGNOSIS OF FABRY DISEASE

The aim of the study was to determine the clinical features and molecular genetic patterns of patients with Fabry disease (FD) to optimize the diagnostic stepwise.&#x0D; Object and methods. The comparison of clinical features was performed and the activity of lysosomal enzyme a–galactosidase A in the peripheral blood leukocyte homogenate was studied in 120 male with the neuropathic pain or acroparesthesia who contacted the Center of Orphan Diseases of NSCH “Ohmatdyt” in years 2002–2016. The cascade family screening (in 8 people) at low enzyme levels and molecular genetic analysis for the presence of mutations in the GLA gene were performed.&#x0D; Results. The activity of –galactosidase A was decreased (range 0.5–12.6 nM/mg/h with median 2.0 nM/mg/h) in nine cases (7.5%). All these patients had additional clinical signs (angiokeratoma, hypertrophic cardiomyopathy, coarse facial features, and compromised family tree). The diagnosis of FD were confirmed by the molecular genetic analysis in the GLA gene; there were identified two new mutations (p.739 740delAA and C.945 946delinsTTGA). The other mutations in 6 out of 8 examined families were revealed by the screening of the first kinship degree female relatives, but the activity of –galactosidase A in leukocytes was only reduced in 4 of them.&#x0D; Conclusion. The multisystem lesions and the difference in the clinical signs of FD complicate the timely formulation of diagnosis. Selective screening among patients with renal insufficiency, cardiac pathology, and ischemic stroke in the anamnesis increases the possibility of FD diagnosis. Cascade family screening of FD patients relatives is highly effective in identification new patients with non–classical form of FD. Inclusion in the selective group of persons with chronic diseases, compromised pedigree, acroparesthesia and additional FD probable clinical signs reduces the range ofpatients for further high–cost testing and optimizes the diagnosis of FD.