Multiple Differential Diagnoses Research Articles

DAO-2, a New Software Tool for Multiple Differential Diagnoses with Probability. Application for the Screening of Rare Anemias in Sardinia

The increasing number of laboratory parameters and diagnostic information makes every day more difficult to remember the entire differential Diagnosis list for all of them. The high prevalence or rare anemias in the island of Sardinia (Italy) makes mandatory to screen the general population for the possible presence of hemoglobinopathies. In fact, the prevalence of Beta Thalassemia goes from 9.1 % of the population in the City of Nuoro to 11.7% in the City of Muravera. The prevalence of Alpha Thalassemia genetic mutations is much more frequent, going from 9.1% in the City of Tempio to 39% in the City of Alghero.DAO-2 is a software tool made using C## (C Sharp) and SQL relational databases, that permit to do Multiple Differential Diagnoses that consist in the Differential Diagnosis of more than one symptom at the same time. After, using the probabilistic theory called Bayes Theorem or Rule of Bayes, gives the probability of every possible disease or medical condition.We have checked the utility of DAO-2 as a software tool for the screening of the rare anemias in Sardinia. The Ospedale Pediatrico Microcitemico is a Hospital a Specialized in thalassemia and other rare anemias. We have cheked the utility of DAO-2 in 394 consecutive patients with a known anemia that came to our hospital and also in 195 persons in that we have excluded the presence of anemia or genetic conditions that predispose to a rare anemia (controls). TableDiagnosticnNON BETA (control)195HbH (alfa thalasemia intermedia)129Thalassemia intermedia Splenectomized33Alfa Thalassemia Trait diag.suspected32Beta Thalassemia Trait30Iron Deficiency Anaemia22Thalassemia intermedia (Beta-Thal Interm)18Alfa Thalassemia Heterozygous14Thrombopenia11microdrepanocitosi (Beta-S)8Thalassemia homozygous (young children Intermedia/Major)7Beta Thal Thalassemia major transfused7HbH (Alfa Thalassemia intermedia) transfused6Hereditary Spherocytosis Splenectomized5Blackfan-Diamond Anemia3Dyserithropoietic Anaemia type I (CDA I)3Sickle cell anaemia3Iron Deficiency Anaemia treated3Piruvate-Kinase deficiency3IRIDA iron-refractory iron deficiency anemia3Beta Thalassemia major3Fanconi’s Anaemia2Dyserithropoietic Anaemia type II (CDA II)2Hyporegenerative anemia2Anemia of Newborn2Megaloblastic Anemia1Piruvate-Kinase deficiency Splenectomized1Hemoglobinopaty (Taybe) + α- thalassemia1Hemoglobinopaty hyperunstable (Hb Cagliari)1Hemoglobinopaty Koln1Hemoglobinopaty E (Hb E)1Hemoglobinopaty G (Hb G-Copenaghen)1Hemoglobinopaty J (Hb J-SARDEGNA)1HbH (alfa thalasemia intermedia) Splenectomized1Leucopenia & Neutropenia1Metahemoglobinemia (MET-Hb)1Pyropoikilocytosis1Evans’s Syndrome1Hereditary Spherocytosis28Delta-Beta Thalassemia (Sardegna)1HbH (alfa thalasemia intermedia) + Beta Thalassemia Trait1Total394The use of this new software, called DAO-2 makes possible to predict in the majority of the cases the presence of a rare anemia or a heterozygous non clinical carrier of genetic changes that can provoke a rare anemia. It is necessary to do prospective studies to check the efficiency of this software before to use it in the clinical practice. DisclosuresNo relevant conflicts of interest to declare.

Musculoskeletal Pain: A New Algorithm for Differential Diagnosis of a Cardinal Symptom in Pediatrics

Musculoskeletal pain (MSP) is a common childhood complaint associated with multiple differential diagnoses, including cancer. Considering the expanding spectrum of diagnostics, evaluat-ing a young patient with MSP is a challenge today, particularly for non-specialists in a primary care setting. Since childhood cancer is rare and most cardinal symptoms mimic rather non-serious diseases, misdiagnosis is not uncommon, but of significant prognostic relevance. To build the appropriate bridge between primary and secon-dary care for a child presenting with MSP, thereby preventing treatment delay and longterm sequelae, initial evaluation should follow a comprehensive, multidisciplinary, systematic and stepwise approach, which unites the patient's individual anamnestic, psychosocial, and clinical charac-teristics. After a systematic review of the literature, we generated multidisciplinarily quality-assured recommendations for efficient, rational and cost-effective primary care assessment of pediatric MSP. The algorithm promotes the identification and structured interpretation of the patient's individual clinical clues. It should serve the primary care physician to recognize when further intervention, rather than reassurance and follow-up, is needed using the minimum amount of testing to make an appropriate, prompt diagnosis in the clinical situation "child presenting with MSP". A German version of this algorithm has been published in the Guideline-Portal of The Association of the Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften", AWMF) in November 2013.

Posterior reversible encephalopathy syndrome

SummaryWe describe a case in which a complicated past medical history, combined with lack of knowledge of a condition, led to a delay in diagnosis. A common presentation with multiple differential diagnoses resulted in a delay in treatment of a condition that is actually simple to treat.

Optic Neuritis and the Evaluation of Visual Impairment in Multiple Sclerosis

This review covers causes of visual impairment in multiple sclerosis (MS), differential diagnosis, and treatment. Emerging technologies are sometimes used in assessing the visual system and may require a neurologist's familiarity. The most common causes are emphasized and discussed in detail, including illustrative cases. The use of optical coherence tomography as both a clinical and research tool has advanced our understanding of how the afferent visual system is affected by MS. Optic neuritis remains one of the most common initial manifestations of MS, although a number of other causes of visual impairment are possible even in the patient with known MS. Some causes of visual impairment are consequences or complications of MS treatment and are particularly important to recognize. Low-contrast letter acuity and optical coherence tomography are techniques or tests emerging from the research arena that may inform care of the patient with MS and are important for the neurologist to be aware of.

Rhabdomyolyse und Erhöhung der Kreatinkinase

Creatine kinase (CK) plays an important role in cellular energy metabolism in various tissues and skeletal muscle is recognized as being the largest reservoir of this enzyme. Elevated CK levels can be induced by various harmless or severe conditions implying multiple differential diagnoses for the physician. Trauma, inflammation, drug-induced toxicity, genetic disorders as well as metabolic, endocrine or rheumatic diseases might lead to cell degeneration and leakage of CK and other cellular components. Massive destruction of muscular tissue leads to rhabdomyolysis, defined as CK elevation combined with organ damage, which requires immediate diagnostic and therapeutic intervention.

From heave to leave: understanding cyclic vomiting syndrome.

Cyclic vomiting syndrome (CVS) is an idiopathic functional gastrointestinal disorder that has been underrecognized in the adult population. Nausea, vomiting, and abdominal pain are common presentations to gastrointestinal nursing. There are multiple differential diagnoses the clinician must consider prior to a diagnosis of CVS to recognize the disorder. CVS occurs in 4 phases: (a) interepisodic, (b) prodromal, (c) vomiting, and (d) recovery. Each phase has specific treatment guidelines. There is no specific "cure" for CVS; proper management is key. Increasing awareness of CVS is paramount to its detection. CVS has been examined in the pediatric population and has often been considered a pediatric disorder. More recently, it has come to be recognized in the adult population. Proper care and management of these patients allow for better support for patients and their families who are often on the primary caregivers. Nurses are often on the front lines of care and knowledge of CVS from the beginning should lead to shortened hospital stays and optimal patient care.

Ensuring Appropriate Expert Testimony for Cases Involving the “Shaken Baby”

Ensuring Appropriate Expert Testimony for Cases Involving the “Shaken Baby”

Dysautonomia after pediatric brain injury

Dysautonomia is an under-recognized and often misdiagnosed condition following acquired brain injury. The condition is largely a diagnosis of exclusion, given that the cardinal signs of the disorder (hyperthermia, hypertension, tachycardia, tachypnoea, diaphoresis associated with muscle overactivity) are relatively non-specific and have multiple differential diagnoses. This has resulted in many clinicians not recognizing the condition, instead diagnosing it as opiate withdrawal or infection (organism not identified). This is not to say that patients with dysautonomia do not get infections, only that not all temperatures are bacterial in origin. Part of the difficulty with the diagnosis of dysautonomia has been a lack of adequate diagnostic criteria. While the use of diagnostic criteria has become more common in recent research, Kirk et al. go one step further than these observational systems by applying a statistical model to determining ‘caseness’. Their predictive model, incorporating hypertension, sweating, and dystonia, provides another means of thinking about the diagnosis of dysautonomia. It is unlikely that this triad will be as useful in an adult rehabilitation population, where data shows that hypertension rarely persists more than 4 weeks post injury. Alternatively, recent research has suggested that over-reactivity to normally non-noxious stimuli is pathognomonic of the condition. Determining diagnostic criteria remains an area of ongoing research. Although under-diagnosed, dysautonomia is a surprisingly common condition. Estimates of the incidence consistently fall around 10% of the sample across adult and paediatric samples, irrespective of whether the research is undertaken in the intensive care unit or in the rehabilitation setting. This high incidence is accompanied by a poorer prognosis across multiple studies, as measured by longer length of stay, poorer rehabilitation outcomes, greater likelihood of requiring longterm institutional care, and higher health care costs. While clinicians often assume that dysautonomia and worse outcome are epiphenomena related to the severity of the patient’s injury (and hence unavoidable), this has yet to be shown in empirical research. Perhaps, controversially, there are multiple reasons to believe that dysautonomia might produce secondary brain damage. As such, it is surprising that the condition has been completely ignored in prospective multicentre ⁄ international traumatic brain injury outcome studies. Furthermore, there is a sufficiently large body of research to suggest that it is inappropriate to ignore treatment of this condition on the basis that dysautonomia ‘burns out’ over time. In a well-designed study of consecutive admissions to a rehabilitation centre, Kirk et al. provide further confirmatory evidence of the importance of the condition. The paper extends the limited paediatric literature on the condition, and in doing so highlights the overlap between the condition in children and that reported in the more extensive adult data set. Furthermore, their data confirms previous suggestions that the incidence of the condition is higher following severe hypoxic brain injury. Thus, while an estimated 80% of dysautonomia cases in world literature result from traumatic brain injury, their work confirms that dysautonomia is three times more common following cardiac arrest; it is only that severe hypoxic brain injury is a less common clinical scenario. While the majority of published research has used the term dysautonomia, this appears to have been for accidental and historical reasons. By definition, the term dysautonomia refers to any abnormality of autonomic function. Unfortunately, the use of such a generic label for a specific syndrome has caused additional confusion for a condition that many clinicians fail to recognize. For this reason, an international expert consensus group that I am chairing is promoting the use of the term paroxysmal sympathetic hyperactivity to identify the key clinical features of the condition.

Diagnosis of Sanfilippo Disease Correlating Clinical, Radiological and Biochemical Findings–A Case Report

Mucopolysaccharidoses (MPS) are a group of genetic diseases and its diagnosis is a challenging task due to multiple differential diagnosis. We had combined clinical findings, radiological and ophthalmological features. Biochemical test for urine glycosaminoglycans (GAG) was done for confirmation of diagnosis in the patient. The case of Sanfilippo disease was characterized by slowly progressive, severe CNS involvement with mild somatic disease. Radiological features were suggestive of Sanfilippo disease and urine GAG test for MPS was positive in the case. With the clinical features we had multiple differential diagnoses. The radiological investigations minimized the list and the biochemical test confirmed GAG in urine. In this case the combination of clinical, radiological and biochemical findings confirmed the diagnosis of Sanfilippo disease.

Myxoid Malignant Fibrous Histiocytoma Presenting as a Midline Nasal Mass

Myxoid malignant fibrous histiocytoma is a rare type of pediatric non-rhabdomyosarcoma soft-tissue sarcoma. The case of a 5-year-old girl is presented, highlighting the potential for multiple pitfalls and aberrant differential diagnoses that need to be identified for successful treatment of pediatric myxofibrosarcomas. An awareness of these tumors and a call for standardized postsurgical treatment protocols is necessary in order to successfully treat children with this disease.

Primary Cutaneous Small- to Medium-Sized CD4+ Pleomorphic T-Cell Lymphoma

Primary cutaneous small- to medium-sized CD4+ pleomorphic T-cell lymphoma (PCSM-TCL) is a rare and provisional subcategory of cutaneous T-cell lymphoma, associated with a favorable prognosis. We present five cases of PCSM-TCL and review the literature to address questions surrounding its diagnosis and treatment. A retrospective review was conducted of 353 patients with non-mycosis fungoides cutaneous lymphomas evaluated at the M.D. Anderson Cancer Center Cutaneous Lymphoma Clinic over 10 years. A retrospective search of the English literature using PubMed was conducted to identify additional cases. Only five patients had a diagnosis of PCSM-TCL. Three patients had unique multifocal presentations that responded well to topical therapy or excision. One patient with localized disease initially treated with radiation therapy had an aggressive relapse requiring systemic therapy. One patient had an isolated nodule that fully resolved with excision. The review of the English literature found 232 additional cases. The presentation of PCSM-TCL was heterogeneous and included solitary/localized papules, nodules, plaques, and tumors. Multiple differential diagnoses were considered and PCSM-TCL diagnosis was based on histopathologic features and clinical correlation. Treatment of solitary/localized lesions included excision or radiation therapy. Multifocal lesions were uncommon and associated with an aggressive course requiring systemic chemotherapy. The heterogeneous presentation, variable histologic overlap with other lymphoproliferative disorders, and uncertain prognosis of PCSM-TCL creates diagnostic and management dilemmas for clinicians. For treatment, a distinction should be made between indolent and aggressive subtypes. Further investigation is needed to determine if PCSM-TCL is indeed a distinct lymphoma category and, additionally, if aggressive subtypes should remain part of the same diagnostic category.

Inflamación idiopática de la órbita en la infancia

Niño de dos años con inflamación idiopática de la órbita que ingresó por edema, rubor y calor en párpados izquierdos. Fue tratado con antibióticos de amplio espectro sin mejoría. Por empeoramiento del cuadro se llevó a cirugía para biopsia del tejido señalado en las imágenes diagnósticas. Por el aspecto macroscópico se inició una prueba terapéutica con corticoesteroides con excelente respuesta. El informe histopatológico reveló inflamación idiopática de la órbita que tiene múltiples diagnósticos diferenciales, los cuales requieren tratamientos diferentes. Se descartaron así otras patologías que pueden comprometer la vida del paciente.

Pilomatrixoma. Review of 205 cases

To determine the incidence and clinical features of patients diagnosed with pilomatrixoma. A retrospective analysis was made of 205 cases of pilomatrixoma diagnosed according to clinical and histological criteria, with an evaluation of the incidence, patient age at presentation, gender, lesion location and size, single or multiple presentation, differential diagnosis, histopathological and clinical findings and relapses. Pilomatrixoma was seen to account for 1.04% of all benign skin lesions. It tended to present in pediatric patients--almost 50% corresponding to individuals under 20 years of age--with a slight male predilection (107/98). Approximately 75% of all cases presented as single lesions measuring less than 15 mm in diameter. Multiple presentations were seen in 2.43% of cases. The most frequent locations were the head and orofacial zones (particularly the parotid region), with over 50% of all cases, followed by the upper (23.9%) and lower limbs (12.7%). Only one relapse was documented following simple lesion excision. The frequency of pilomatrixomas was 1.04% of all benign skin lesions--the lesions being predominantly located in the maxillofacial area. Due to the benign features of this disorder, simple removal of the lesion is considered to be the treatment of choice, and is associated with a very low relapse rate.

HB E/β0 Thalassemia can present with normal phenotype

Sir, Hb E is the second most common hemoglobin variant in the world with a high frequency in SE Asia reaching a frequency from 15% to 50% in Thailand, Burma, Srilanka, and Vietnam as the most common hemoglobin variant. Hemoglobin E/β°Thalassemia, however, resembles homozygous β°Thalassemia both clinically and hematologically. Heterozygous HbE diseases are asymptomatic with mild hypochromia that is prevalent in Bengal, Assam, and in East India. Homozygous suffer from mild hemolytic anemia and have modest splenomegally with target cell 25-50%. HbE diseases entity often goes unnoticed as most of the cases have no noticeable clinical findings as reviewed extensively by Wasi in Thailand.[1–5] A 6 years old girl presented with progressively increasing generalized weakness, difficulty in walking with breathlessness, withdrawn at home, poor appetite since her third birthday. Family history or other histories revealed no significant related events of regular intake of blood. The girl was moderately pale, mild icteric with mesomorphic features with an apparently normal look for her age and sex with mild hepatosplenomegally. No dysmorphic feature (mega hepatosplenomegally or bronzy discoloration of skin or typical facial changes) suggestive of chronic or congenital hematological diseases was present to bring the child under multiple differential diagnoses. Pulse oxymetry showed 91% oxygen saturation. Hemoglobin level was 4 g% with few reticulocytes, numerous hypochromic nucleated red cells, and microcytes with almost no normal appearing red cells on smear, occasional spherocytes present, more than 50% red cells being the target cells. MCV was 50-66 fL and serum bilirubin 1.84 mg%, unconjugated 1.4, conjugated 0.4. The hemoglobin agar gel electrophoresis at pH 8.6 showed Hb E in the same position as Hb C and Hb A2. At pH 6.3, Hb E ran with Hb A; HbA 0.2 g (5.8%), HbF 1.8 g (44.1%), HbE 2.0 g (50.1%). The caregivers were counseled with the ‘live with a disease’ philosophy and the diagnosis as well as prognosis of this disease was carefully explained in the line of management of β°Thalassemia. It is very important to generate awareness among our fraternity regarding subtle presentation and importance of early detection of E/β°Thalassemia and that timely intervention can help in better prognosis. Professionals related to community pediatrics, clinical epidemiology, and community genetics, functioning in unison, has a dominant role to play in preventing the fatal outcome of this genetic disorder.

Spécificités des crises d’épilepsie chez le sujet âgé : proposition d’un score électro-radioclinique d’orientation

Diagnosis of epileptic seizure may be difficult in older patients because seizure manifestations are often unusual: confusion, paresis… and because there are multiple differential diagnoses (syncope, transient ischemic attack, transient global amnesia…). To promote and facilitate the diagnosis of seizures in the elderly, neurologists and gerontologists must work together and focus their strategy on two points: firstly, the knowledge of the specific presentation of seizures in elderly patients, and secondly, the adoption of a reasoning based on seizures and not epileptic syndromes. A multidisciplinary group worked on epilepsy of the elderly to elaborate an electro-clinical score which aims to help establish the diagnosis of epilepsy in elderly patients in different clinical settings. This electro-clinical score is based on a systematic review of scientific literature and the recommendations are explicitly linked to supporting evidence. Further, clinical validation of the electro-clinical score is required.

Fetal Alcohol Spectrum Disorders and Their Persisting Sequelae in Adult Life: Monocausal Discussion

The article mentions the fetal alcohol spectrum disorders as the most common cause of learning deficiencies and points out the associated long term sequelae. In my opinion, the problems are discussed in too monocausal a fashion, and the multiple differential diagnoses of mental-cognitive developmental disorders are not elucidated sufficiently. These include primary brain system disruptions, sequelae of extremely premature birth, and psychosocial influences. Unilateral explanations can lead to unjustified blaming and false stigmatisation. To diagnose and care for these children, for the past 20 years Germany has had 130 socialpediatric centers nationwide, about 200 000 children and adolescents with developmental abnormalities and impairments of all kinds are being treated in these centres every year. Interdisciplinary multi-purpose diagnostic tests that consider the etiology, initiation of treatment, and long term care are being given in these centers by pediatricians in collaboration with complementary therapists, psychologists, and social consultants.

Erupções vesicopustulosas benignas no neonato

As erupções vesicopustulosas neonatais compreendem um grupo de desordens que surgem nas primeiras quatro semanas de vida. Apresentam extensa relação de diagnósticos diferenciais e, na maioria das vezes, podem ser identificadas clinicamente ou mediante recursos laboratoriais simples. Os dermatologistas devem reconhecer esses quadros cutâneos e, sobretudo, saber diferenciá-los de outras dermatoses graves e potencialmente fatais.

Use of Magnetic Resonance Imaging in Predicting Further Vascular Events Among Patients With Transient Ischemic Attacks

To the Editor: In the October 2004 issue of Stroke , Purroy et al reported a higher risk of further vascular events among transient ischemic attack (TIA) patients with diffusion-weighted imaging (DWI) acute ischemic lesions.1 They prospectively studied 83 patients with TIA and suggested that duration of symptoms (>60 minutes), presence of DWI acute ischemic lesion, and large vessels disease were important risk factors for the recurrence of vascular events, including cerebrovascular ones. However, only a minority (9.6%) of patients had their magnetic resonance imaging performed (MRI) within 2 days of symptom onset.1 As quoted by the authors, 10.5% of patients with TIA will have a stroke within the next 90 days of their TIA, and 25% to 50% of these have their stroke within the first 24 to 48 hours.2,3 Therefore, a substantial portion of MRI data may show a second cerebrovascular ischemic event instead of the first stroke/TIA and subsequently do not predict the primary outcome. We would like to know the proportion of clinically defined early/late new vascular events. Second, the inclusion of TIA as a primary endpoint is problematic and not conventional in relation to stroke prevention trials.4–8 The percentage of patients with TIA versus stroke at outcome should be stated. Third, a significant proportion of patients presented with vertebrobasilar (43.4%) TIA. What symptoms were accepted as diagnosis of vertebrobasilar TIA? Isolated “dizziness” of unclear origin, for example, is sometimes diagnosed as possible vertebrobasilar TIA but has multiple alternate differential diagnoses that may not ever be conclusively determined. It would have been interesting to know the proportion of vertebrobasilar and carotid TIA among patients with DWI acute ischemic lesions and further vascular events. Fourth, …

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Evidence of a Lyme borreliosis infection from the viewpoint of laboratory medicine

More than 20 years after the first description of the pathogen Borrelia burgdorferi the diagnosis of Lyme borreliosis is based primarily on clinical criteria. Multiple differential diagnoses have to be considered and laboratory confirmation based on various test procedures is required until now. For screening assays the immunofluorescence assay (IFA), enzyme linked immunoassay (EIA), or indirect hemagglutination assay (IHA) are frequently in use. During the last ten years a stepwise diagnostic procedure in USA and Europe has been recommended. The use of a serological screening assay as the first diagnostic step, followed by a confirmatory assay only in the case of a positive or borderline result of the screening assay is now “state of the art”. The most frequently used method is a sensitive enzyme linked immunoassay followed by a sensitive and specific immunoblot technique. However, the quality of these indirect serological tests and, most importantly, the interpretation criteria of the commercial tests vary dramatically. The choice of Borrelia strains, antigen preparation, production conditions and test procedures vary widely. The immunoblot, used as a confirmatory assay, must meet the highest quality standards but in practice under routine laboratory conditions, these levels are often not reached. The major reason for this “shortcoming” is that Lyme borreliosis is not a sexually transmitted disease and no official approval has been required by the commercial suppliers so far. Another increasingly important aspect is the introduction of molecular biological assays into laboratory routines. Numerous authors published many articles about the usefulness of polymerase chain reaction as a diagnostic tool for the detection of borreliae in human specimens. However, a routine method has not yet been established. Furthermore, no standardized method for DNA isolation from different human specimens has been developed so far. For this reason PCR is not accepted as a routine method and the application should be restricted to a few laboratories with experience in the field of Lyme borreliosis. In summary, it is important to inform clinicians about the limitations of the tests used and it would be very helpful to stage a European or worldwide conference to establish accepted rules for the diagnosis of Lyme borreliosis.