The correct answer is 1. Wiskott-Aldrich syndrome associates immunodeficiency, thrombopenia and atopic dermatitis with the immunological study described in the statement.

[HIDDEN] Wiskott-Aldrich syndrome associates immunodeficiency, thrombopenia and atopic dermatitis with the immunological study described in the statement.

A 2-year-old boy, his personal history includes: 3 episodes of acute otitis media, 1 meningococcal meningitis and 2 pneumonias (one middle lobe and one left upper lobe). She has been admitted on 3 occasions for thrombopenic purpura (on three occasions antiplatelet antibodies were negative and bone marrow showed normal megakaryocytes). Several males of the maternal family had died in childhood due to infectious processes. The examination showed typical lesions of atopic dermatitis. The immunological study showed a slight decrease in T lymphocyte subpopulations; elevated IgA and IgE; decreased IgM and IgG at the lower limit of normal. What is the most likely diagnosis?

Transient hypogammaglobulinemia of infancy.

Severe X-associated combined immunodeficiency.

A case of IgG subclass deficiency with the initial presentation of transient hypogammaimmuno-globulinemia of infancy and a review of IgG subclass deficiencies.

Primary immunodeficiency diseases are not common in children. The possibility of an immunological defect should be considered in any individual with repeated infections. A definite diagnosis for immodeficiency is sometimes difficult to achieve because of overlapping clinical manifestations. Immunoglobulin subclass deficiency is an immunological deficiency disease with which, one or more IgG subclasses are deficient. T cell immunity is normal. Patients may develop recurrent bacterial and respiratory infections or could remain asymptomatic. The authors report a case of immunoglobulin G subclass deficiency presenting initially as transient hypogammaglobulinemia of infancy. A 2 month-old boy presented to Siriraj Hospital with a history of chronic protracted diarrhea, disseminated scabies and sepsis. On presentation, he had generalized scaly and maculopapular rash with no palpable lymph nodes. CBC revealed WBC 22,100 cells/cm3 with PMN 42 per cent, lymphocytes 38 per cent, Eosinophils 4 per cent, Basophil 2 per cent and platelets 254,000/cm3. The immunoglobulin levels were as follows: IgG 181 mg/dl, IgA < 6.6 mg/dl, IgM 26.3 mg/dl. Lymphocyte enumerations revealed CD4 of 2,433 cells/cm3 (N 1,460-5,160); CD8 4,682 cells/cm3 (N 650-2,450); CD19 1,588 cell/cm3 (N 500-1,500); CD16 230 cell/cm3 (N 573 +/- 264). The initial diagnosis was X-linked agammaglobulinemia vs common variable immunodeficiency disease. His diarrhea and five courses of sepsis responded well to antibiotics administration and courses of intravenous immunoglobulin (IVIG) replacement. His through IgG became normal at 2 years of age (after 12 months of IVIG). IVIG was stopped and the diagnosis was changed to transient hypogammaglobulinemia of infancy (THI). Nevertheless, during his 4 month follow-up he developed recurrent sinopulmonary infections (i.e, otitis media and pneumonia). Repeated immunoglobulin profile showed IgG 1,200 mg/dl, IgA 135 mg/dl, IgM 26 mg/dl, IgG subclass were IgG, 1,030 mg/dl (N 280-830), IgG2 30 mg/dl (N 40-2,400), IgG3 22 mg/dl (N 6-130), IgG4 3 mg/dl (N 3-120). A diagnosis of IgG2 subclass deficiency presenting early as transient hypogammaglobulinemia of infancy was then made. Treatment with monthly IVIG was reinitiated and the patient is currently doing well. The authors present a case of IgG subclass deficiency presenting as transient hypogammaglbulinemia of infancy. Follow-up of the immune profile and clinical manifestation is necessary for a definite diagnosis.

[Wiskott-Aldrich syndrome].

The Wiskott-Aldrich syndrome is a primary immunodeficiency characterized by congenital microthrombocytopenia, eczema and recurrent infections. This paper reports the case of a 3-year-6-month male patient, whose maternal uncle died at the age of 3 months due to fulminant sepsis from a pulmonary infection. The patient was a product of the first pregnancy, he was born at 27 weeks' gestation and weighed 1,400 g. As a neonate he was hospitalized during the first 2 months of life because of a low gastrointestinal bleeding, thrombocytopenia and severe infections. In the next 4 months and before coming to our hospital the infant was hospitalized 54 times. On admission he presented disseminated dermatosis, enlarged neck lymph nodes and psychomotor retardation. Laboratory studies revealed hemoglobin 8.1 g/dL, platelets 31,000/uL, mean platelet volume 5.6 fL, IgM 39.3 mg/dL, IgA 67 mg/dL, IgG 1,380 mg/dL. On several occasions he received globular packages and platelet concentrates. The infusion of immunoglobulin G was started every 21 days. Bone marrow transplantation was delayed due to the complications that merited 13 hospitalizations and severe thrombocytopenia, low gastrointestinal bleeding, septic arthritis, infectious gastroenteritis, chronic suppurative otitis media and severe folliculitis. At the age of 4 years BMT of cord was performed, and 26 days after transplantation he presented septic shock and died. The prognosis of bone marrow transplantation in Wiskott-Aldrich syndrome and in other primary immunodeficiencies depends on the promptness of its performance at early stages in life. It is important that the first contact physicians be aware of the primary immunodeficiency signs and symptoms.

De novo mutation causing X-linked hyper-IgM syndrome: a family study in Taiwan.

X-linked hyper-IgM syndrome (XHIM) is a rare primary immunodeficiency disorder caused by mutations of the gene encoding the CD40 ligand (CD40L). It is characterized by recurrent infections with markedly decreased serum IgG, IgA and IgE levels but normal or elevated IgM levels. We report the clinical manifestations and complete immune studies in the first family with molecularly proven XHIM in Taiwan. A 5-month-old boy presented with rapidly progressive pneumonia which responded poorly to antibiotics. High levels of IgM and very low levels of IgG, IgA, and IgE were noted in his plasma specimen: IgM, 128 mg/dl; IgG, 18 mg/dl; IgA, 4 mg/dl); IgE, 1 IU/ml. Whole blood flow cytometry when he was 21 months old showed that only a small percentage (0.48%) of his in vitro-activated CD4+ T cells expressed CD40L. When he was 3 years old, repeated flow cytometry showed essentially the same result (0.4%), compared with his father's CD40L expression of over 85%. The patient's mother had moderately decreased CD40L expression (74.4%). Hyper-IgM syndrome was confirmed by CD40L mutation analysis in the boy, which revealed a Lys 96 stop (nucleotide A307T) in exon 2 of CD40L, with a truncated protein resulting in the loss of the entire TNF domain. His mother was a carrier and apparently the individual in whom the mutation originated. Eleven other family members, including the patient's father, sister, and grandmother, and the mother's sisters and their children, all had normal results on CD40L mutation analysis. The patient has remained without significant bacterial infection on a regimen of monthly IVIG infusion and oral trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia (PCP) prophylaxis, although he has had recurrent oral ulcers and neutropenia. Bone marrow transplantation is planned.

Wiskott-Aldrich syndrome complicated by an atypical lymphoproliferative disorder: a case report.

Wiskott-Aldrich syndrome (WAS) is an X-linked syndrome consisting of eczema, recurrent pyogenic infection, and thrombocytopenia with decreased platelet volume. Immunologic studies reveal normal immunoglobulin G (IgG), decreased IgM, elevated IgA and IgE levels, and decreased T-cell function. Patients with WAS often have increased susceptibility to lymphoproliferative disorders (LPDs). We report a 3-year-old boy who had persistent thrombocytopenia with bleeding, recurrent infections, and chronic eczema with frequent skin infections since birth. A blood smear revealed small platelets (50% of normal size). Immunologic studies showed normal IgG (1880 mg/dL), decreased IgM (76 mg/dL) and increased IgA (228 mg/dL) and IgE (14,282 IU/mL) levels. The relative proportions of immune cells were CD2 52.2%, CD3 41.1%, CD4 23.4%, CD8 16.8%, CD19 8.0%, CD57 7.7% and active T cells 14.6%. T-cell dysfunction was detected on the multitest for cell-mediated immunity. The WAS diagnosis was confirmed by mutation analysis which demonstrated a 4-base pair deletion in WAS protein gene exon 1. His thrombocytopenia was uncontrolled despite intravenous immunoglobulin infusions, so splenectomy was performed. The platelet count then rose to about 60,000 to 80,000/microL. However, about 2 weeks after splenectomy, he developed generalized lymphadenopathy and lymphoma was misdiagnosed based on lymph node biopsy at another hospital where he was admitted for urgent care. However, our analysis of his lymph node pathology led to the diagnosis of atypical LPD (ALPD). The lymphadenopathy regressed spontaneously 1 month later without chemotherapy. Early and correct diagnosis of WAS complicated with ALPD is important to avoid unnecessary chemotherapy.

Recurrent pneumonia as warning manifestation for suspecting primary immunodeficiencies in children.

Two hundred and eight children with recurrent pneumonia were studied over a 5-year period. Among these patients we found 10 cases with primary immunodeficiency disease: 6 cases of IgA deficiency, 1 case of X-linked agammaglobulinemia, 1 case of common variable immunodeficiency, 1 case of hyper IgM syndrome, and 1 case of Wiskott-Aldrich syndrome. This study describes the clinical features of these cases and assesses the usefulness of our immunodeficiency screening protocol. In this group 6 were males; the mean age at first episode of pneumonia was 3 years (range 3 months to 18 years), and the age of diagnosis ranged between 10 months and 19 years. The average number of episodes of pneumonia in each patient was 5 (range 2 to 12), and the number of hospitalizations ranged up to 13. The etiologic agents isolated from this recurrent pneumonia were S. pneumoniae, Moraxella, adenovirus, respiratory syncytial virus, and influenza B virus. Intravenous immunoglobulin was used in four cases. Two patients had chronic pulmonary damage with bronchiectasis and interstitial pneumonia. Only one patient died (Wiskott-Aldrich syndrome) during the follow-up from an intracranial hemorrhage. We found that the screening protocol applied to patients with recurrent pneumonia is a useful tool for ruling out the primary immunodeficiency disorders.

[Satisfactory evolution of a patient diagnosed in childhood with Bruton's disease].

Bruton's agammaglobulinemia is a primary immunodeficiency with a disease onset during the first months of age, when the maternal serum immunoglobulin levels decrease. It is characterized by recurrent infections and agammaglobulinemia. We report the case of a 6-year-old male patient with third-degree consanguinity, product of a third pregnancy and complete immunization scheme. He had a history of oral candidiasis at the age of 3 months, chicken pox at the age of 7 months, and two episodes of complicated bronchopneumonia at the age of 1 year and 6 years. He was admitted to the hospital because of fever and cough. Examination of the chest showed rales and right basilar hypoventilation, and a blood cell count revealed leukocytosis and neutrophilia. The diagnosis of pneumonia was made. He was treated with IV antibiotics. Serum immunoglobulins were reported to be low (IgM 55 mg/dL, IgA 0.9 mg/dL, and IgG 199 mg/dL). With these findings the clinical diagnosis of X-linked agammaglobulinemia (ALX) was concluded. A molecular test was performed fining a BTK gene confirming the diagnosis of Bruton's disease. Therapy with intravenous IgG was started every 21 days. During his evolution, he presented three episodes of rhinosinusitis, one of suppurative otitis media, and four events of pneumonia that required 37 days of hospitalization. After hospital discharge, the patient was free of infections and he returned to his daily activities. In cases of recurrent and severe respiratory infections in children, we must consider primary immunodeficiency disease in the differential diagnosis, mainly antibiotic deficiency. Early diagnosis and treatment improves the survival and quality of life in these patients.

Hyper-IgM syndrome: report of one case.

The hyper-IgM syndrome (HIM) is a rare primary immunodeficiency disorder caused by defects in the CD40 ligand (CD40L)/CD40-signaling pathway. It is characterized by recurrent infections with markedly decreased IgG, IgA and IgE levels but normal or elevated serum IgM levels. A 5-month-old boy presented with rapidly progressive pneumonia which responded poorly to antibiotics. High levels of IgM and very low levels of IgG, IgE and IgA were noted in his plasma specimen (IgM, 128 mg/dl; IgG, 18 mg/dl; IgE, 1 IU/ml; IgA, 4 mg/dl). The relative proportions of immune cells were CD3 24.6%, CD4 10.3%, CD8 2.2%, CD19 30.2%, CD57 1.0% and active T cells 1.1%. After IVIG treatment, the pneumonia improved. Repeat assessment at the age of 15 months showed IgM decreased to the normal range (32 mg/dl). Whole blood flow cytometry assay for CD40L expression confirmed the diagnosis of hyper-lgM syndrome when he was 21 months old. Only a small percentage (0.48%) of the patient's in vitro activated CD4+ T cells expressed CD40L, compared with 33.54% from a healthy control. The patient's father, mother and sister all had a normal CD40L expression activation patterns (43.52%, 40.78%, 34.11%, respectively). On a regimen of monthly IVIG infusion and oral trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia (PCP) prophylaxis, the patient has had no recurrent infections.

Serum IgD and IgE concentrations in immunodeficiency diseases.

Concentrations of IgD and IgE were measured in sera from 165 patients with well-defined immunodeficiency in an effort to find information possibly relevant to the roles of antibodies of these classes in host defense. Values for both immunoglobulins were generally quite low in patients who had marked deficiencies of all three major immunoglobulins, although occasional normal or high normal values for IgD were seen in hypogammaglobulinemic patients. Group mean IgD concentrations were also depressed in patients with Wiskott-Aldrich syndrome and in those with selective IgA deficiency; IgE concentrations were depressed in patients with X-linked immunodeficiency with hyper-IgM and in those with ataxia telangiectasia. IgD and IgE were both significantly elevated in patients with extreme hyperimmunoglobulinemia E and undue susceptibility to infection and in a patient with the Nezelof syndrome; none of these patients had histories suggestive of atopy. In addition, the mean IgE concentration was significantly elevated in patients with selective IgA deficiency, many of whom were atopic, and in those with the Wiskott-Aldrich syndrome. The highest IgD concentration (163 mg/100 ml) was found in serum from a boy with variable immunodeficiency who had a lifelong history of severe recurrent pharyngeal infections, primarily streptococcal in etiology. Recurrent staphylococcal infection was a feature common to many but not all patients with elevated serum IgE concentration. These data may prove useful in the future delineation of biologic roles for antibodies in these two immunoglobulin classes.

[Hypogammaglobulinemia G and A with hypergammaglobulinemia M. Apropos of 12 cases].

Hyper IgM with low IgG and IgA is a rare humoral immunodeficiency. We presently report 12 new observations which have been clinically and immunologically studied. On one occasion the syndrome was found to be associated with congenital rubella. Since 10/12 children were male, X-linked inheritance is suggested which has been confirmed in 2 cases. In most cases (9/12), the first infections occurred within the first year of life. The syndrome is causing upper and lower respiratory tract infections due to bacteria, as well as gut infections. Lymphoid organ hyperplasia has been noted in 11/12 patients. Polyclonal hyper IgM serum contrasts with low or absent IgG, IgA and IgE. In some instances, some IgM antibody response was detected. A dysfunction of cellular immunity was not detected. Autoimmunity was detected in 3 patients. Finally, transient neutropenia occurred in 50% of the patients. Intravenous immunoglobulin G substitution treatment resulted in a significant reduction in the occurrence of infections as well as in normalization of growth rate. Immunoglobulin infusion also frequently induced correction of hyper IgM and neutropenia.

List of primary immunodeficiencies

Normal numbers of B cells with decreased IgG and IgA and increased IgM: Hyper-IgM syndromes Normal numbers of B cells with isotype or light chain deficiencies: heavy chain deletions, kappa chain deficiency, isolated IgG subclass deficiency, IgA with IgG subclass deficiency, selective immunoglobulin A deficiency Specific antibody deficiency to specific antigens with normal B cell and normal Ig concentrations Transient hypogammaglobulinemia of infancy (THI)

Wiskott–Aldrich syndrome

Signs and symptoms WAS occurs most often in males due to its X-linked recessive pattern of inheritance, affecting between 1 to 10 males per million. The first signs are usually petechiae and bruising, resulting from a low platelet count (i.e. thrombocytopenia). Spontaneous nose bleeds and bloody diarrhea are also common and eczema typically develops within the first month of life. Recurrent bacterial infections typically develop by three months of age. The majority of children with WAS develop at least one autoimmune disorder, and cancers (mainly lymphoma and leukemia) develop in up to a third of patients. Immunoglobulin M (IgM) levels are reduced, IgA and IgE are elevated, and IgG levels can be normal, reduced, or elevated. In addition to thrombocytopenia, WAS patients have abnormally small platelets (i.e. microthrombocytes) and ~30% also have elevated eosinophil counts (i.e. eosinophilia).

Wiskott–Aldrich syndrome

Diagnosis The diagnosis can be made on the basis of clinical findings, the peripheral blood smear, and low immunoglobulin levels. Typically, IgM levels are low, IgA levels are elevated, and IgE levels may be elevated; paraproteins are occasionally observed. Skin immunologic testing (allergy testing) may reveal hyposensitivity. Individuals with Wiskott–Aldrich syndrome however are at higher risk for severe food allergies. Not all patients have a positive family history of the disorder; new mutations do occur. Often, leukemia may be suspected on the basis of low platelets and infections, and bone marrow biopsy may be performed. Decreased levels of WASp are typically observed. The current gold standard for diagnosis is DNA sequence analysis, which can detect WAS and the related disorders XLT and XLN in 95% of patients and carriers.

Hypogammaglobulinemia

of primary immunodeficiency (PID). These different forms can affect different parts of the immune system, including immunoglobulin production. Primary immunodeficiencies usually have a delay of several years between initial clinical presentation and diagnosis. Some primary immune deficiencies include ataxia-telangiectasia (A-T), autosomal recessive agammaglobulinemia (ARA), common variable immunodeficiency (CVID), hyper-IgM syndromes, IgG subclass deficiency, isolated non-IgG immunoglobulin deficiencies, severe combined immunodeficiency (SCID), specific antibody deficiency (SAD), Wiskott-Aldrich syndrome, or X-linked agammaglobulinemia. CVID is the most common form of primary immunodeficiency. SCID is considered a medical emergency and suspected cases require immediate specialist center referral for diagnosis and treatment. It is more often that hypogammaglobulinemia develops as a result of another condition, which are called secondary or acquired immune deficiencies. These

X-linked agammaglobulinemia

Signs and symptoms Affects males 50% of the time if mother is a carrier for the gene. Children are generally asymptomatic until 6–9 months of age when maternal IgG decreases. Present with recurrent infections with Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, hepatitis virus, and enterovirus CNS infections. Examination shows lymphoid hypoplasia (tonsils and adenoids, no splenomegaly or lymphadenopathy). There is significant decrease in all immunoglobulins. Genetics Most antibodies are gamma globulins. Antibodies are made mainly by plasma cells, which are daughter cells of the B cell line. The Btk enzyme plays an essential role in the maturation of B cells in the bone marrow, and when mutated, immature pro-B lymphocytes are unable to develop into pre-B lymphocytes, which normally develop into mature (naive) B cells that leave the bone marrow into the blood stream.

Antibody Deficiency Disorder -- Differential Diagnosis

The most important differential diagnosis includes the following: X-linked agammaglobulinemia characterizes by recurrent bacterial infections in boys, and genetic studies may reveal the presence of Bruton tyrosine kinase (BTK) mutations. Transient hypogammaglobulinemia of newborns presents in newborns above the age of 4 months and characterizes by recurrent pneumonia, meningitis, otitis media, and other problems that resemble Bruton disease. It is a physiological defect in the immune system caused by maternal IgG disappearance and corrected soon but requires treatment. In super-IgM syndrome, recurrent bacterial infections occur, but the cause of this illness is a mutation in the gene encoding for CD40 on T lymphocytes that causes a failure in T and B lymphocyte cooperation. Common variable immunodeficiency presents with recurrent bacterial infections, including sinopulmonary problems but later in life (second-fourth decade), and the diagnosis is made once all causes of immunodeficiency have been ruled out. [6] [7] [21] [33]

Biochemistry, Immunoglobulin M -- Clinical Significance -- Selective IgM Deficiency

Selective IgM deficiency (SIGMD) is a rare disorder with fewer than 300 cases reported. SIGMD is associated with an isolated deficiency in IgM in the presence of normal levels of other immunoglobulins such as IgG and IgA and normal levels of T cells and other leukocytes. [12] Individuals with SIGMD may be asymptomatic, or they may suffer from recurring infections from encapsulated bacteria (e.g., S. pneumoniae and H. influenzae ) in addition to viral infections. Additionally, SIGMD can be associated with malignancy, autoimmunity, or allergy. SIGMD may occur as a secondary effect of another disease, such as malignancy or bacteremia. Yet, primary causes of SIGMD have also been described, as some are associated with deletions on chromosome 22, for example. [12] The diagnosis of SIGMD is one of exclusion. Other diseases that result in low levels of multiple isotypes must be excluded, such as common variable immunodeficiency or X-linked agammaglobulinemia, which will likely result in reduced levels of several antibody isotypes. Conversely, Wiskott-Aldrich syndrome is often associated with low IgM yet elevated levels of IgG and IgA. Cold Agglutinin Disease

Humoral immune deficiency

Absent B cells with a resultant severe reduction of all types of antibody: X-linked agammaglobulinemia (btk deficiency, or Bruton's agammaglobulinemia), μ-Heavy chain deficiency, l 5 deficiency, Igα deficiency, BLNK deficiency, thymoma with immunodeficiency B cells low but present, but with reduction in 2 or more isotypes (usually IgG & IgA, sometimes IgM): common variable immunodeficiency (CVID), ICOS deficiency, CD19 deficiency, TACI (TNFRSF13B) deficiency, BAFF receptor deficiency. Normal numbers of B cells with decreased IgG and IgA and increased IgM: Hyper-IgM syndromes Normal numbers of B cells with isotype or light chain deficiencies: heavy chain deletions, kappa chain deficiency, isolated IgG subclass deficiency, IgA with IgG subsclass deficiency, selective immunoglobulin A deficiency Transient hypogammaglobulinemia of infancy (THI)

List of skin conditions

Bare lymphocyte syndrome Chronic granulomatous disease (Bridges–Good syndrome, chronic granulomatous disorder, Quie syndrome) Common variable immunodeficiency (acquired hypogammaglobulinemia) Complement deficiency DiGeorge syndrome (DiGeorge anomaly, thymic hypoplasia) Graft-versus-host disease Griscelli syndrome Hyper-IgE syndrome (Buckley syndrome, Job syndrome) Immunodeficiency with hyper-IgM Immunodeficiency–centromeric instability–facial anomalies syndrome (ICF syndrome) Isolated IgA deficiency Isolated primary IgM deficiency Janus kinase 3 deficiency Leukocyte adhesion molecule deficiency LIG4 syndrome Myeloperoxidase deficiency Neutrophil immunodeficiency syndrome Nezelof syndrome (thymic dysplasia with normal immunoglobulins) Omenn syndrome Purine nucleoside phosphorylase deficiency Severe combined immunodeficiency (alymphocytosis, Glanzmann–Riniker syndrome, severe mixed immunodeficiency syndrome, thymic alymphoplasia) Shwachman–Bodian–Diamond syndrome

[Hyper-IgM syndrome in a boy with recurrent pneumonia and hepatosplenomegaly].

We present a boy diagnosed at age 14 years with hyper-immunoglobulin (Ig) M syndrome, a congenital immunodeficiency characterized by reduced plasma concentrations of IgA, IgE and IgG, with normal or elevated concentrations of IgM. This syndrome is caused by a defect of CD40 ligand (CD40L) on T-helper lymphocytes, impeding the "second signal" during activation of B lymphocytes and interactions of T cells with dendritic cells and macrophages, resulting in the absence of secondary immune response (class switching, affinity maturation, immune memory), as well as responses to T-dependent antigens, with an impairment of cellular immunity. The history of the presented patient was dominated by frequent lower respiratory infections and failure to thrive. Physical examination demonstrated severe hepatosplenomegaly. The suspicion of hyper-IgM syndrome was raised by low plasma IgA (0.36 g/l) with high plasma IgM (35.5 g/l), while the concentration of IgG was within the normal range (12.1 g/l). The diagnosis was confirmed by flow cytometry, which demonstrated the absence of expression of CD40L on lymphocytes following stimulation by phorbolmyristylacetate and calcium ionophore. Since the time of diagnosis, intravenous immunoglobulin therapy has led to catch-up growth, recession of hepatosplenomegaly and reduction in the frequency of respiratory infections. Our report emphasizes the importance for the primary healthcare paediatrician to be well informed about the clinical presentation and pathogenesis of hyper-IgM syndrome, in order to provide early detection and increase the likelihood of success in treating this rare immunodeficiency. To the best of our knowledge, this is the first case of hyper-IgM syndrome reported in the Republic of Serbia.

List of primary immunodeficiencies

Predominantly antibody deficiencies In primary antibody deficiencies, one or more isotypes of immunoglobulin are decreased or don't function properly. These proteins, generated by plasma cells, normally bind to pathogens, targeting them for destruction. Absent B cells with a resultant severe reduction of all types of antibody: X-linked agammaglobulinemia (btk deficiency, or Bruton's agammaglobulinemia), μ-Heavy chain deficiency, l 5 deficiency, Igα deficiency, BLNK deficiency, thymoma with immunodeficiency B cells low but present or normal, but with reduction in 2 or more isotypes (usually IgG & IgA, sometimes IgM): common variable immunodeficiency (CVID), CD19 deficiency, TACI (TNFRSF13B) deficiency, BAFF receptor deficiency. Normal numbers of B cells with decreased IgG and IgA and increased IgM: Hyper-IgM syndromes

Common variable immunodeficiency

Diagnosis According to a European registry study, the mean age at onset of symptoms was 26.3 years old. As per the criteria laid out by ESID (European Society for Immunodeficiencies) and PAGID (Pan-American Group for Immunodeficiency), CVID is diagnosed if: the person presents with a marked decrease of serum IgG levels (<4.5 g/L) and a marked decrease below the lower limit of normal for age in at least one of the isotypes IgM or IgA; the person is four years of age or older; the person lacks antibody immune response to protein antigens or immunization. Diagnosis is chiefly by exclusion, i.e. alternative causes of hypogammaglobulinemia, such as X-linked agammaglobulinemia, must be excluded before a diagnosis of CVID can be made.

Bone and joint disease associated with primary immune deficiencies.

Primary immune deficiencies (PIDs) are characterized by functional and/or quantitative abnormalities of one or more immune system components. Several bone and joint abnormalities can occur in patients with PID, with arthritis being the most common. Joint manifestations, of which arthritis is the most common, occur chiefly in humoral PIDs (agammaglobulinemia, common variable immunodeficiency, hyper-IgM syndromes, and IgA deficiency) and occasionally in other PIDs (chronic granulomatous disease and Wiskott-Aldrich syndrome). Monoarthritis or oligoarthritis is the usual pattern, although polyarthritis may occur, occasionally with nodules suggesting rheumatoid arthritis. Arthritis in patients with PID is usually infectious in nature, the most common causative organism being Mycoplasma, followed by Staphylococcus, Streptococcus, and Haemophilus. These bacteria can induce not only synovial infections, but also aseptic arthritogenic inflammatory responses. Arthritis having no demonstrable relation to chronic infection has been reported also and ascribed to dysimmunity-driven mechanisms that exhibit a number of specific features. Bone lesions are far less common and usually due to infections complicating humoral PID. Distinctive bone manifestations occur in a number of rare PIDs (e.g., hyper-IgE syndrome and Di George syndrome) and in syndromes characterized by spondyloepiphyseal dysplasia. Familiarity with PID syndromes both enhances the diagnostic capabilities of physicians and provides insight into the pathophysiology of bone and joint abnormalities associated with immune dysfunction. In children and occasionally in adults, a combination of bone and/or joint manifestations and hypogammaglobulinemia may indicate PID. When there is no evidence of lymphoproliferative disease, infection, or iatrogenic complications, investigations for PID should be obtained. PID-related arthritis is a unique model for studying the pathogenesis of presumably postinfectious arthritis and of inflammatory joint diseases including rheumatoid arthritis.

List of skin conditions

Severe combined immunodeficiency (alymphocytosis, Glanzmann–Riniker syndrome, severe mixed immunodeficiency syndrome, thymic alymphoplasia) Shwachman–Bodian–Diamond syndrome Thymoma with immunodeficiency (Good syndrome) Transient hypogammaglobulinemia of infancy Warts–hypogammaglobulinemia–infections–myelokathexis syndrome (WHIM syndrome) Wiskott–Aldrich syndrome X-linked agammaglobulinemia (Bruton syndrome, sex-linked agammaglobulinemia) X-linked hyper-IgM syndrome X-linked hypogammaglobulinemia X-linked lymphoproliferative disease (Duncan's disease) X-linked neutropenia

Early bone marrow transplantation in an infant with Wiskott-Aldrich syndrome.

The Wiskott-Aldrich Syndrome (WAS) is a rare X-linked immunohematological disorder characterized by eczema, profound thrombocytopenia, and progressive immunodeficiency. Severe hemorrhage, overwhelming sepsis, or lymphoreticular malignancy usually cause death in childhood. Recently, bone marrow transplantation (BMT) has been curative in some well-established cases, but there is no general agreement about the place of BMT in infants with WAS before the development of significant immunological abnormalities. We describe the successful use of early histocompatible BMT in a 10-month-old infant in whom WAS was diagnosed on the basis of eczema, thrombocytopenia, small platelets, and raised serum immunoglobulin A (Ig) and IgE, but before the development of immunodeficiency as evidenced clinically by recurrent infections, or immunologically by low serum IgM or consistently abnormal lymphocyte responses to mitogens. After an unstable period for several weeks posttransplantation when he developed marked hepatomegaly and severe interstitial pneumonitis, he made a good recovery. His eczema and thrombocytopenia resolved and he has shown no clinical or laboratory evidence of immunodeficiency. It is now over 2 years since his BMT. Because of the poor prognosis of WAS, where a histocompatible donor is available, BMT at the earliest opportunity, despite the inherent risks of such a procedure, may be the best option for an infant with WAS.

Severe combined immunodeficiency with B-lymphocytes (T-B+SCID): report of two cases.

Severe combined immunodeficiency (SCID) is a rare pediatric medical emergency in Taiwan. The early diagnosis of infants with SCID is very important because it can save the life of these critical infants. The essential clues important for early diagnosis of SCID patients include positive family history of early infant death, paucity of tonsil and lymphoid tissue, cutaneous fungal infection and lymphopenia. Severe combined immunodeficiency is a heterogeneous group of inherited disorders characterized by the failure of both cellular and humoral immunity. It can be categorized into SCID with B-lymphocytes predominant (T-B+SCID) and SCID with paucity of B-lymphocytes (T-B-SCID), according to the number of B-lymphocytes in the patient's peripheral circulation. We report two male infants with T-B+SCID who had been suffering from severe pulmonary distress with persistent O2 desaturation when they were transferred to our pediatric intensive care unit. Tracing back these infant's family histories, it was discovered that both of them had an elder brother who had died to overwhelming infection within the first year of life, and Pneumocystis carinii pneumonitis (PCP) was confirmed in the elder brother of case 2. After hospitalization, the immune condition of these two infants were evaluated which showed a decrease in T-cell and NK cell number, an increase in B-cell number, and decreased serum levels of all the Igs except IgM, which was elevated in case 1. These were the diagnostic immunological findings for T-B+SCID, which included X-linked SCID and Jak-3-deficient SCID. During hospitalization, severe mucocutaneous candidiasis and PCP were noted and confirmed in case 1 and PCP was highly suspected in case 2. Bone marrow transplantation, the only curable treatment for T-B+SCID at present, could not be performed in these two patients because of their grave clinical condition. Both of them expired due to their progressively downhill pulmonary conditions.

Update of the Wiskott-Aldrich syndrome. From a new case report.

After presenting the case of a male patient who was diagnosed as suffering from the Wiskott-Aldrich syndrome at the age of 4 months, we review the main clinical (infections, bleeding and eczema), immunological (deficiency of IgM, normal IgG, elevated IgA and IgE, deficiency of total T lymphocytes, normal T4 levels, decreased levels of T8, diminished response to phytohemagglutinin and partial depletion of the lymphocyte population in biopsies of lymph nodes and spleen) and haematological (thrombocytopenia, dysmegakaryocytosis, decreased half-life and decreased granulation in the protoplasm of megakaryocytes) manifestations of this syndrome. In general, our aim is to carry out an up-to-date review of the syndrome, and to include comments on the diagnostic and therapeutic aspects.

Immune disorder

Primary immune deficiencies Severe combined immunodeficiency (SCID) DiGeorge syndrome Hyperimmunoglobulin E syndrome (also known as Job's Syndrome) Common variable immunodeficiency (CVID): B-cell levels are normal in circulation but with decreased production of IgG throughout the years, so it is the only primary immune disorder that presents onset in the late teens years. Chronic granulomatous disease (CGD): a deficiency in NADPH oxidase enzyme, which causes failure to generate oxygen radicals. Classical recurrent infection from catalase positive bacteria and fungi. Wiskott–Aldrich syndrome (WAS) Autoimmune lymphoproliferative syndrome (ALPS) Hyper IgM syndrome: X-linked disorder that causes a deficiency in the production of CD40 ligand on activated T-cells. This increases the production and release of IgM into circulation. The B-cell and T-cell numbers are within normal limits. Increased susceptibility to extracellular bacteria and opportunistic infections.

[Clinical features and genotype analysis of 132 patients with Wiskott-Aldrich syndrome].

To investigate the clinical and immunological laboratory features, gene mutations, treatment and prognosis in children with Wiskott-Aldrich syndrome (WAS). The clinical, laboratory characteristics, treatment and prognosis of 132 children with WAS, who visited Children's Hospital of Chongqing Medical University from April 2000 to June 2015, were analyzed retrospectively. All patients were male. The median age of disease onset was 15 days and the median age at diagnosis was 10 months. Of the 132 cases, 112 had classic WAS, 20 had X-linked thrombocytopenia (XLT). The median platelet count was 23×10(9)/L. All cases had the clinical characteristics of WAS including bleeding, eczema, and being susceptible to infection. The initial symptoms include hemorrhage (75.0%) and eczema (16.7%). Twenty-one cases had autoimmune diseases and one patient had leukemia. WAS protein (WASP) expression in 115 cases were measured by flow cytometry, 88 cases were negative, in 12 cases WASP decreased, in 5 cases it was normal, 10 cases had bimodal distribution. Eighty-one kinds of mutations were found in 122 families, including eight kinds of hot-spot mutations, which were 290 C> N / 291G> N (R86C / H / L), 665 C> T (R211X), 155 C> T (R41X), 168 C> T (T45 M), IVS1+ 1 g> t/ a, IVS6 + 5 g> a, IVS8 + 1 g> a and IVS8 + 1to + 6del gtga. Meantime, 29 kinds of novel mutations were found, which were 321T>C, 415C>A, 471C>T, 102-105delC, 521 del C, 1330 del A, IVS2-2 a>c, 168 C>A/1412 C> T, exon1-2 del/1412 C>T, and so on. The proportion of CD3(+) T cells (31.3%), helper T cells (37.3%) and cytotoxic T cells (38.6%) in the peripheral blood declined. The serum levels of IgG (51.1%), IgA (43.3%) and IgE (40.0%) increased, IgM (25.6%) decreased. Of the 132 cases, 72 remain survived, of whom 36 cases received hematopoietic stem cell transplantation (HSCT), 14 patients with classic WAS received intravenous immunoglobulin (IVIG) therapy. With regular IVIG therapy, the frequency of infections was reduced and the patients' symptoms were improved. The clinical characteristics of Wiskott-Aldrich syndrome were early age of onset, microthrombocytopenia, eczema and recurrent infections. The proportion of T lymphocyte declined, the serum levels of IgG, IgA, and IgE increased, and level of IgM decreased in a part of patients. The detection of WAS gene mutation and WAS protein detection was the key diagnostic methods. Regular IVIG can gain more time for children who will receive HSCT and improve their quality of life.

Hyper-IgM syndrome type 2

Hyper IgM Syndrome Type 2 is a rare disease. Unlike other hyper-IgM syndromes, Type 2 patients identified thus far did not present with a history of opportunistic infections. One would expect opportunistic infections in any immunodeficiency syndrome. The responsible genetic lesion is in the AICDA gene found at 12p13. Hyper IgM syndromes Hyper IgM syndromes is a group of primary immune deficiency disorders characterized by defective CD40 signaling; via B cells affecting class switch recombination (CSR) and somatic hypermutation. Immunoglobulin (Ig) class switch recombination deficiencies are characterized by elevated serum IgM levels and a considerable deficiency in Immunoglobulins G (IgG), A (IgA) and E (IgE). As a consequence, people with HIGM have an increased susceptibility to infections.

Pediatrics_Nelson

Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by hypogammaglobulinemia developing after an initial period of normal immune function, most commonly in the second and third decades of life (see Table 73-1). Serum IgG levels are less than 500 mg/dL (usually <300 mg/dL) with IgA levels less than 10 mg/dL and/or low IgM levels. Antibody titers to protein antigens, suchas tetanus and diphtheria, and to polysaccharide antigens,such as pneumococcus, are low or absent. T-cell numbersand function are highly variable, and B-cell numbers can be normal or low. Patients exhibit normal-sized or enlargedtonsils and lymph nodes and may have splenomegaly. Theyare susceptible to frequent respiratory tract infections due to Streptococcus pneumoniae, Haemophilus influenzae type b, and Mycoplasma. Gastrointestinal infections with Giardia, Campylobacter, Salmonella, Helicobacter, and enteroviruses are common. Autoimmune hemolytic anemia and thrombocytopenia occur

[Common variable immunodeficiency. Review].

Common variable immunodeficiency (CVI) is a primary immunodeficiency characterized by deficient antibody production. The cause of this immunodeficiency is unknown; several in vitro studies have revealed a significant number of alterations that could explain the hypogammaglobulinemia present in this syndrome. Among those described are primary B cell alterations, numerical and functional T cell abnormalities, and defects in the interaction between accessory cells. The alteration typical of CVI is the failure of B lymphocytes to differentiate from antibody-producing cells, resulting in deficient immunoglobulin secretion. Among the T cell abnormalities described are a diminished proliferative response to mitogens and antigens, alterations in the level of production of several cytokines, especially reduction in the production of IL-2, diminished antigen-specific T cells and increase basal apoptosis after stimulation. Antigen presenting cells, monocytes and dendritic cells can also present alterations and contribute to deficient antigen response. The clinical manifestations of these patients is variable; most present recurrent bacterial infections due to encapsulated bacteria, especially sinusitis, otitis, bronchitis, and pneumonias. A few patients can present mycobacterial or fungal infection and occasionally Pneumocystis carinii. Viral infection is uncommon in these patients although some suffer recurrent herpes zoster infection. Clinical features of septicemia and central nervous system infections are less frequent. The incidence of digestive tract infections in these patients is high. The most common cause of diarrhea is Giardia lamblia; Salmonella, Shigella and Campylobacter are also common pathogens. Autoimmune disease is also more prevalent in these patients than in the general population. The most frequently associated diseases are hemolytic anemia, idiopathic thrombocytopenic purpura and autoimmune neutropenia. Cancer is also frequently associated with CVI, the most common forms being lymphoproliferative syndromes, especially non-Hodgkin's lymphoma. Granulomas are a unusual manifestation in some patients with CVI; their localization varies but the most commonly affected organs are the spleen and lungs. Some authors have compared these granulomas with those characterizing sarcoidosis, especially when appearing in the lung. Diagnosis of CVI is usually by exclusion of other diseases, such as cystic fibrosis, immotile cilia syndrome or allergic processes. CVI should be suspected in all patients with recurrent bacterial infections especially those localized in the respiratory tract. Other primary immunodeficiencies which present clinical findings similar to CVI and which should be ruled out are selective IgG subclass deficiency, IgA deficiency and selective deficiency in the response to polysaccharide antigens with normal immunoglobulin levels. The serum hypogammaglobulinemia present in all patients with CVI provides the diagnostic key. The age at which clinical manifestations appear, the absence of familial antecedents and the presence of circulating B lymphocytes form the basis of the differential diagnosis between X-linked agammaglobulinemia and autosomal recessive forms. The treatment of choice of patients with CVI is treatment with human gamma-globulin. Currently, the most common route of administration is intravenous; these molecules have a half-life of approximately 21 days and a high degree of safety concerning the possible transmission of viral infections. Adverse reactions are generally few and clinically unimportant. The most frequently used doses oscillate between 200 and 400 mg/kg body weight every 2-4 weeks. Both the dose and its frequency should be personalized for each patient. Early diagnosis of patients with CVI, application of treatment with appropriate antibiotics for infections and treatment with gamma-globulins prevent long-term complications of this disease and dramatically improve the quality of life and life expectancy of these patients.

First_Aid_Step2

Combined (continued) Wiskott-Aldrich syndrome An X-linked disorder with less severe Band T-cell dysfunction. Patients have eczema, ↑ IgE/IgA, ↓ IgM, and thrombocytopenia. The classic presentation involves bleeding, eczema, and recurrent otitis media. ↑↑ risk of atopic disorders, lymphoma/leukemia, and infection from S. pneumoniae, S. aureus, and H. inﬂ uenzae type b. Phagocytic Chronic granulomatous disease (CGD) Leukocyte adhesion def ciency Chédiak-Higashi syndrome An X-linked (2/3) or autosomal-recessive (1/3) disease with def cient superoxide production by PMNs and macrophages. Anemia, lymphadenopathy, and hypergamma-globulinemia may be present. A defect in the chemotaxis of leukocytes. An autosomal-recessive disorder that leads to Chronic skin, pulmonary, GI, and urinary tract infections; osteomyelitis and hepatitis. Infecting organisms are catalase . ↑ risk of infection with Aspergillus. May have granulomas of the skin and GI/GU tracts. Recurrent skin, mucosal, and pulmonary


It is possibly a temporal arteritis, the clinical picture and a CBC with increased reactants are enough to confirm the suspicion. Then an ocular evaluation should be done to rule out AIN, urgent treatment should be instituted (if there is AIN, 3 boluses of methylprednisolone 1 g, if there is not, prednisone mg/kg) and biopsy should be evaluated.

It is possibly a temporal arteritis, the clinical picture and a CBC with increased reactants are enough to confirm the suspicion. Then an ocular evaluation should be done to rule out AIN, urgent treatment should be instituted (if there is AIN, [HIDDEN], if there is not, prednisone mg/kg) and biopsy should be evaluated.

A 70-year-old woman with a history of anorexia, weight loss, muscle and proximal joint discomfort and pain in the temporomandibular region comes to the emergency department for unilateral vision loss (hand movement), sudden and painless onset (afferent pupillary defect). What test would you order first for diagnostic purposes?

Lessons to be learned: a case study approach--a case of temporal arteritis.

A 71-year-old male presented with a history of sudden partial visual loss in the right eye with an inferior visual field defect over the past 3-4 days. He had no history of headache or of facial pain. Clinical examination confirmed that vision on the right side was reduced to 6/18 and on the left to 6/12. The right eye showed a relative afferent pupillary defect. There was no other abnormality of the anterior segment of either eye. The right retina showed a pale swollen optic disc and a provisional diagnosis of anterior ischaemic optic neuropathy (AION) was made. An urgent erythrocyte sedimentation rate (ESR) was ordered and the patient was asked to return to the eye clinic in one month. However, 16 days later--when it was first recognised that his ESR was elevated to 75 mm in the first hour--the patient was recalled immediately in order to commence systemic steroid treatment; but regrettably, by this time, his right eye had become totally blind. In this case, although the attending doctor made a correct clinical diagnosis on presentation, he failed to act upon the result of the blood test.

InternalMed_Harrison

A careful neurologic examination is an essential first step in the evaluation. In most cases, patients with an abnormal examination or a history of recent-onset headache should be evaluated by a computed tomography (CT) or magnetic resonance imaging (MRI) study. As an initial screening procedure for intracranial pathology in this setting, CT and MRI methods appear to be equally sensitive. In some circumstances, a lumbar puncture (LP) is also required, unless a benign etiology can be otherwise established. A general evaluation of acute headache might include cranial arteries by palpation; cervical spine by Pain induced by bending, lifting, cough Pain associated with local tenderness, e.g., region of temporal artery the effect of passive movement of the head and by imaging; the investigation of cardiovascular and renal status by blood pressure monitoring and urine examination; and eyes by funduscopy, intraocular pressure measurement, and refraction.

Atypical retinal vaso-occlusion with structural and functional resolution.

The purpose is to report a patient with primary open-angle glaucoma that developed sudden painless unilateral vision loss, a sequential ophthalmoscopic appearance with features of both central retinal artery and later central retinal vein occlusion, and objective visual system dysfunction in the form of a relative afferent pupil defect, who spontaneously recovered vision along with complete resolution of the pupillary defect over several weeks. A 50-year-old woman with a long-standing history of glaucoma presented with acute, painless vision loss in one eye, a pallid retina with a cherry red macula, diffuse retinal hemorrhages, and a relative afferent pupil defect. Spectral domain optical coherence tomography and fluorescein angiography were essentially normal with neither retinal edema nor retinal ischemia to account for the visual dysfunction. Over the course of 2 months, the patient regained vision and the relative afferent pupil defect, typically a permanent manifestation of retinal destruction, resolved. Not all retinal vaso-occlusive phenomena can be completely attributed to a central retinal vein or artery occlusion. In the patient presented, there was no objective diagnostic testing that revealed a cause for the patient's vision loss or relative afferent pupillary defect. This combined with the complete recovery of vision and resolution of the relative afferent pupillary defect underscores a lack of comprehensive understanding of retinal vaso-occlusive disease.

First_Aid_Step2

If a 20-year-old female develops headaches after drinking red wine, think migraine. Associated symptoms/signs: Significant findings include fever or rash (consider meningitis or other infectious causes), jaw claudication (specific for temporal arteritis), or constitutional symptoms such as weight loss (associated with neoplastic, inﬂammatory, or infectious conditions). Photophobia, nausea, and vomiting are associated with migraine, aneurysmal SAH, and meningitis, but neck stiffness is more likely to accompany the latter two. Neurologic sequelae: Look for diplopia, mental status changes or associated symptoms (numbness, weakness, dizziness, ataxia, visual disturbances), papilledema, or pupillary abnormalities (partial CN III palsy or Horner’s syndrome). Patient risk factors: High-risk patients are > 50 years of age, immunocompromised, or with preexisting malignancy. If SAH is suspected, obtain a head CT without contrast. If CT is , LP is mandatory. Obtain a CBC.

Ultrasound-Assisted Diagnosis of Optic Neuritis in the Emergency Department: A Case Report.

Optic neuritis is a common cause of subacute unilateral vision loss, occurring in 1-5 per 100,000 persons per year. It is more common in Caucasians, women, and those from countries with northern latitudes. Those aged 20-49 years are at greatest risk. The condition arises due to inflammation of the optic nerve. Inflammation may occur due to systemic inflammatory disorders, most commonly multiple sclerosis. A 21-year-old African-American male presented to our emergency department with a complaint of painful unilateral vision loss. On examination he was found to have a relative afferent pupillary defect and red desaturation. A bedside ultrasound suggested pseudopapilledema suggestive of optic neuritis. He was admitted to Neurology for confirmation of and treatment for optic neuritis. Magnetic resonance imaging confirmed optic neuritis. The patient was treated with i.v. steroids and discharged after improvement in visual function. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Optic neuritis is a clinical diagnosis. The subtle historical components and examination findings make it a diagnostic challenge for the busy emergency physician. Early diagnosis may improve visual outcomes. Discovery of pseudopapilledema on bedside ultrasound may be seen in optic neuritis, and is another finding that emergency physicians may assess for in patient presenting with unilateral vision loss.

Masticatory muscle pain: an important indicator of giant cell arteritis.

Giant cell arteritis (GCA) is a polysymptomatic disease which constitutes an ophthalmic emergency because early recognition and management can prevent blindness. There is conflicting information in the literature on the validity, sensitivity, and specificity of various systemic symptoms and signs of GCA. This paper presents a review of our prospective studies on the subject, and our findings are particularly relevant to dentists. We investigated 363 patients in a prospective study. Positive temporal artery biopsy was seen in 106 patients and negative in 257 referred for diagnosis of GCA. Systemic symptoms and signs of GCA and erythrocyte sedimentation rate (Westergren-ESR) and C-reactive protein (CRP) levels were compared in these two groups of patients. The odds of having a positive temporal artery biopsy (i.e., GCA) were 9.1 times greater with jaw claudication (pain in masticatory muscles on eating), 3.4 times with neck pain, 3.2 times with CRP > 2.45 mg/dL, 2.0 times with ESR 47.107 mm/hr, 2.7 times with ESR > 107 mm/hr, and 2.0 times when the patients were aged > or = 75 years. Other signs and symptoms did not show a significant association with a positive biopsy. Our study showed that "normal" ESR values do not rule out GCA but that CRP is a more useful test than ESR. Since jaw claudication is one of the most important symptoms of GCA, dentists should keep this possibility in mind when older patients come complaining of jaw pain while eating.

Childhood-Onset Leber Hereditary Optic Neuropathy: Particular Features.

Leber hereditary optic neuropathy (LHON) is an optic neuropathy of mitochondrial inheritance. Childhood-onset disease is relatively rare and there are limited data on this important patient subgroup. We present 3 particular presentations of LHON. Patient 1 was an 8-year-old boy admitted to the emergency department reporting a progressive bilateral visual loss and intermittent headaches. Neuro-ophthalmological examination revealed a bilateral pseudopapilledema. Lumbar puncture identified intracranial hypertension and the brain and orbits magnetic resonance imaging showed T2 hyperintensity in the posterior region of the left optic nerve and the optic chiasm. Patient 2 was a 12-year-old boy admitted to the emergency department reporting painless, progressive central vision loss in the right eye. Fundus examination revealed a hyperemic disc and vascular network papillary and peripapillary vascular microdilations. Three months later, the left eye presented visual loss. Patient 3 was a 6-year-old female child referred to the neuro-ophthalmology specialist due to painless central visual loss in both eyes. Her BCVA was 1/10 and counting fingers in right and left eye, respectively, and fundus examination revealed a pallor optic disc in the temporal sector. The phenotype of childhood-onset disease may present itself distinct from classical adult-onset LHON. The absence of classical clinical features could lead to initial misdiagnosis. There should exist a high index of suspicion in children presenting unexplained subnormal vision in order to avoid potential diagnostic delays.

First_Aid_Step2

Also called giant cell arteritis; due to subacute granulomatous inﬂ ammation of the large vessels, including the aorta, external carotid (especially the temporal branch), and vertebral arteries. The most feared manifestation is blindness 2° to occlusion of the central retinal artery (a branch of the internal carotid artery). Risk factors include polymyalgia rheumatica (affects almost half of TA patients), age > 50, and female gender. Presents with new headache (unilateral or bilateral); scalp pain and temporal tenderness; and jaw claudication. Fever, permanent monocular blindness, weight loss, and myalgias/arthralgias (especially of the shoulders and hips) are also seen. ESR > 50 (usually > 100). Ophthalmologic evaluation. Temporal artery biopsy: Look for thrombosis; necrosis of the media; and lymphocytes, plasma cells, and giant cells.

Atypical Leber hereditary optic neuropathy with a 34-year interval between vision loss in both eyes.

Leber hereditary optic neuropathy (LHON) is an inherited mitochondrial disease characterized by painless vision loss affecting both eyes. The disease usually develops in both eyes within weeks to months of onset. We report a case of LHON who presented with unilateral vision loss in childhood with an interval of more than 30 years between vision loss in the two eyes. A 43-year-old man presented with a 1-month history of vision loss in his right eye. At 9 years of age, his visual acuity in the left eye declined, and he had been treated with glaucoma eyedrops bilaterally at his eye clinic. At his first visit to our hospital, his BCVA was 0.15 in the right eye and 0.1 in the left eye, and critical flicker frequency was 16 Hz in the right eye and 15 Hz in the left eye, and he was negative for a relative afferent pupillary defect. The Goldman visual field showed central scotoma in both eyes. Fundus examination revealed slight redness of the right optic disc with meandering retinal small vessels, and the left optic disc had a slight pallor. Fluorescein angiography could not be performed because of liver dysfunction. OCT showed prominent bilateral thinning of the RNFL and retinal ganglion cell layer. Enhancement of the optic nerve was not apparent on orbital gadolinium-enhanced magnetic resonance imaging. Hematologic analysis revealed macrocytic anemia and low levels of vitamin B12 and folate. His mother had a presumptive diagnosis of LHON but did not receive genetic testing. A male cousin also had severe vision loss. Based on the likely family history of LHON, we performed genetic testing, which revealed the 11778 mitochondrial point mutation associated with this condition. We report a case of LHON with 34 years interval in vision loss in the fellow eye. LHON may develop in the second eye decades after its onset in the first. Detailed medical interviews and scrutiny, such as examination of family history, are warranted in consideration of LHON.

[Temporal arteritis presenting with headache and abducens nerve palsy. Report of a case].

A 71-year-old man visited our clinic with a 3-day history of severe throbbing headache and 1-day history of horizontal diplopia. He had had jaw claudication and pain in the neck and shoulder several days previously. His right eye was slightly esotropic and did not move laterally. There was no blepharoptosis, proptosis, lid edema, or conjunctival injection. The pupils were unremarkable. The remainder of the cranial nerve functions was intact. There was no limb weakness or sensory impairment. Superficial temporal arteries were swollen and tender on both sides. Laboratory examination showed elevated CRP level and high erythrocyte sedimentation rate. Cranial MR images were unremarkable. The cerebrospinal fluid was acellular with 45 mg/dl of protein. A diagnosis of temporal arteritis was made. Treatment with 50 mg of prednisolone brought about prompt disappearance of the headache. Right ocular movement fully recovered in 10 days. Temporal artery biopsy findings and response to corticosteroid were consistent with temporal arteritis. The motility pattern of the right eye was consistent with complete abducens nerve palsy, which is a rare manifestation of temporal arteritis. Although temporal arteritis is a rare cause of ophthalmoplegia in the elderly patients, swift diagnosis and treatment is necessary to avoid blindness.

A tearfully painful darkness.

A 70-year-old woman presented with new onset of left eye and facial pain. Ophthalmic and neurological examinations, magnetic resonance imaging brain, erythrocyte sedimentation rate, and C-reactive protein were unrevealing. A few days later, she developed vision loss in her left eye. Examination revealed decreased visual acuity with a relative afferent pupillary defect in the left eye and a diffuse mild swelling of the left optic nerve head. Repeat magnetic resonance imaging showed T2 hyperintensity and enhancement of the intraorbital optic nerve and surrounding tissues with no other intracranial abnormalities. Serum studies showed elevated myelin oligodendrocyte glycoprotein IgG titer. She was treated with IV methylprednisolone 1000 mg daily for 3 days and was discharged on prolonged prednisone taper with return of vision to baseline.

Anterior ischemic optic neuropathy due to giant cell arteritis with normal inflammatory markers.

In anterior ischemic optic neuropathy (AION), it is important not to miss the diagnosis of giant cell arteritis (GCA) because this requires immediate steroid treatment to prevent involvement of the second eye and possible blindness. A missed diagnosis also might lead to fatal systemic complications. Observational case report. A 79-year-old woman noticed decreased visual and visual field loss in the right eye. At presentation, right visual acuity was 10/20 (ETDRS chart 2000). There was a right relative afferent pupillary defect of 0.6 log units. Asked for symptoms of GCA she complained about temporal and occipital headache, jaw claudication combined with malaise, and myalgia of the upper limbs. Laboratory tests showed normal inflammatory markers. Repeated tests confirmed ESR and CRP to be within the normal range. GCA being suspected, ultrasound of the superficial temporal arteries and temporal artery biopsy were performed unilaterally on the right side. Histology showed a chronic inflammatory cell infiltrate consistent with active GCA. The patient was treated with high-dose corticosteroids (250 mg methylprednisolone, three times/day, initially) and symptoms rapidly resolved, but visual loss remained unchanged. The case presented here proves that GCA with typical related visual loss (AION) is possible even when both ESR and CRP are in the normal range. Therefore, in the presence of typical symptoms, the clinician must not rely solely on laboratory testing, but start steroid therapy immediately and order a temporal artery biopsy.

Paracentral Acute Middle Maculopathy After COVID-19 Disease: Multimodal Evaluation.

To report the case and multimodal imaging findings of a healthy young woman who developed paracentral acute middle maculopathy (PAMM) 9 weeks after COVID-19 disease. Case report. Ultra-widefield fundus photography, macular spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography (FA), and OCT-angiography (OCT-A) were performed. A 36-year-old woman who developed PAMM 9 weeks after SARS-CoV-2 infection. A 36-year-old woman went to the emergency department (ED) with sudden, painless, left eye (LE) vision loss. The only relevant past medical history was COVID-19 disease 9 weeks before. Best corrected visual acuity (BCVA) was 20/200, a LE relative afferent pupillary defect (RAPD) was present and superficial hemorrhages throughout the macular area and peripheral retina were found. Nearly four hours after admission, LE BCVA recovered to 20/20 without RAPD. Five days after presentation in the ED, the patient returned with recurrent LE vision loss, with spontaneous recovery within 12 hours. Macular SD-OCT revealed hyperreflectivity of the inner plexiform and inner nuclear layers and the diagnosis of PAMM was established. The patient started oral acetylsalicylic acid and oral prednisolone. The patient did not report any new episodes of vision loss and there was a progressive resolution of abnormal fundus findings. SARS-CoV-2 infection increases the risk of vascular thrombotic events with possible involvement of the retinal circulation, and PAMM may present as a possible complication. Ophthalmologists should be able to recognize it promptly through multimodal imaging findings.

[Blindness in both eyes due to late diagnosis of giant cell arteritis].

Giant cell arteritis (GCA) is often diagnosed very late, variable "facets" of the disease exist render the diagnosis more difficult. Follow-up observations of five very old patients are reported in whom diagnosis was made too late, resulting in blindness of both eyes. Five patients (age 76-84 years, 4 women, one man) with GCA became blind in both eyes because diagnosis had been delayed (two patients) or onset of therapy was too late (three patients). In two patients who also had arterial hypertension, the symptom "headache" had been misleading. Symptoms of accompanying general diseases masked the real diagnosis, particularly in the second patient who had renal insufficiency, coronary artery disease, and unilateral obstruction of the internal carotid artery. Symptoms that failed to lead to the correct diagnosis were: muscle or chewing pain (three patients), circumscribed numbness around the mouth (second patient), and persistent headache despite normalization of blood pressure. Normal findings from cranial CTAs (two patients) led to the wrong reassurance of the patient. Swelling of the optic disk (two patients) was misdiagnosed by ophthalmologists, as was a retinal branch arterial occlusion (first patient). Three patients, afraid of possible side effects caused by glucocorticoids, took ineffective alternative medications. Poor vigilance led to blindness of the fifth patient with long-standing polymyalgia rheumatica. Targeted examinations at the onset of symptoms are necessary. GCA-symptoms were mis-constructed by additional diseases that disguised the correct diagnosis. The danger of bilateral blindness is particularly great in patients of great age.

Posterior ischemic optic neuropathy

Defective light perception in one eye causes an asymmetrical pupillary constriction reflex called the afferent pupillary defect (APD). Arteritic PION A-PION most commonly affects Caucasian women, with an average age of 73. At onset vision loss is unilateral, but without treatment it rapidly progresses to involve both eyes. Vision loss is usually severe, ranging from counting fingers to no light perception. Associated symptoms are jaw pain exacerbated by chewing, scalp tenderness, shoulder and hip pain, headache and fatigue. Perioperative PION Vision loss is usually apparent upon waking from general anesthesia. Signs observable to a bystander include long surgery duration and facial swelling. Vision loss is usually bilateral and severe, ranging from counting fingers to no light perception. Cause

[A 62-year-old man with an acute onset of consciousness disturbances].

We report a 62-year-old man who developed coma and died in a fulminant course. The patient was well until May 1, 1996 when he noted chillness, tenderness in his shoulders, and he went to bed without having his lunch and dinner. In the early morning of May 2, his families found him unresponsive and snoring; he was brought into the ER of our hospital. He had histories of hypertension, gout, and hyperlipidemia since 42 years of the age. On admission, his blood pressure was 120/70, heart rate 102 and regular, and body temperature 36.3 degrees C. His respiration was regular and he was not cyanotic. Low pitch rhonchi was heard in his right lower lung field. Otherwise general physical examination was unremarkable. Neurologic examination revealed that he was somnolent and he was only able to respond to simple questions such as opening eyes and grasping the examiner's hand, but he was unable to respond verbally. The optic discs were flat; the right pupil was slightly larger than the left, but both reacted to light. He showed ptosis on the left side, conjugate deviation of eyes to the left, and right facial paresis. The oculocephalic response and the corneal reflex were present. His right extremities were paralyzed and did not respond to pain Deep tendon reflexes were exaggerated on the right side and the plantar response was extensor on the right. No meningeal signs were present. Laboratory examination revealed the following abnormalities; WBC 18,400/ml, GOT 131 IU/l GPT 50 IU/l, CK616 IU/l, BUN 30 mg/dl, Cr 2.1 mg/ dl, glucose 339 mg/dl, and CRP 27.4 mg/dl. ECG showed sinus tachycardia and ST elevation in II, III and a VF leads and abnormal q waves in I, V5, and V6 leads. Chest X-ray revealed cardiac enlargement but the lung fields were clear. Cranial CT scan revealed low density areas in the left middle cerebral and left posterior cerebral artery territories. The patient was treated with intravenous glycerol infusion and other supportive measures. At 2: 10 AM on May 3, he developed sudden hypotension and cardiopulmonary arrest. He was pronounced dead at 3:45 AM. The patient was discussed in a neurological CPC, and the chief discussant arrived at the conclusion that the patient had acute myocardial infarction involving the inferior and the true posterior walls and left internal carotid embolism from a mural thrombus. Post mortem examination revealed occlusion of the circumflex branch of the left coronary artery due to atherom plaque rupture and myocardial infarction involving the posterior and the lateral wall with a rupture in the postero-lateral wall. Marked atheromatous changes were seen in the left internal carotid, the middle cerebral and the basilar arteries; the left internal carotid and the middle cerebral arteries were almost occluded by thrombi and blood coagulate. The territories of the left middle cerebral and the occipital arteries were infarcted; but the left thalamic area was spared. The neuropathologist concluded that the infarction was thrombotic origin not an embolic one as the atherosclerotic changes were severe. Cardiac rupture appeared to be the cause of terminal sudden hypotension and cardiopulmonary arrest. It appears likely that a vegetation which had been attached to the aortic valve induced thromboembolic occlusion of the left internal carotid artery which had already been markedly sclerotic by atherosclerosis. It is also possible that the vegetations in the aortic valve came from mural thrombi at the site of acute myocardial infarction, as no bacteria were found in those vegetations.

Sciatica

Cancer should be suspected if there is previous history of it, unexplained weight loss, or unremitting pain. Spinal epidural abscess is more common among those with diabetes mellitus or immunocompromised or who had spinal surgery, injection or catheter; it typically causes fever, leukocytosis and increased erythrocyte sedimentation rate. If cancer or spinal epidural abscess are suspected, urgent magnetic resonance imaging is recommended for confirmation. Proximal diabetic neuropathy typically affects middle aged and older people with well-controlled type-2 diabetes mellitus; onset is sudden causing pain usually in multiple dermatomes quickly followed by weakness. Diagnosis typically involves electromyography and lumbar puncture. Shingles is more common among the elderly and immunocompromised; usually (but not always) pain is followed by appearance of a rash with small blisters along a single dermatome. Acute Lyme radiculopathy may follow a history of outdoor activities during warmer

[Arteriitis temporalis--a major disease developing in advance age (author's transl)].

Arteriitis temporalis, a disease that was largely unknown in the early fifties, has gained importance in recent years. In the past ten years 32 patients suffering from arteriitis temporalis were diagnosed and treated both in the eye hospital and in the rheumatic-cardiological hospital of the Berlin-Buch Municipal Hospital. The following clinical findings were essential for the diagnosis: advanced or old age of the patient, massive headache in the temporal and/or occipital regions, myalgia primarily in the shoulders and the neck that responded relatively poorly to treatment, reduced eyesight, loss of weight and decrease in vitality. Extremely high BSR, an increased amount of alpha-2 and an increased level of alkaline phosphatase were most important among the laboratory findings. Corticosteroids have proved to be the medicine of choice for treating this condition.

Ankylosing spondylitis

These diagnostic criteria include: Inflammatory back pain:Chronic, inflammatory back pain is defined when at least four out of five of the following parameters are present: (1) Age of onset below 40 years old, (2) insidious onset, (3) improvement with exercise, (4) no improvement with rest, and (5) pain at night (with improvement upon getting up) Past history of inflammation in the joints, heels, or tendon-bone attachments Family history for axial spondyloarthritis or other associated rheumatic/autoimmune conditions Positive for the biomarker HLA-B27 Good response to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) Signs of elevated inflammation (C-reactive protein and erythrocyte sedimentation rate) Manifestation of psoriasis, inflammatory bowel disease, or inflammation of the eye (uveitis) If these criteria still do not give a compelling diagnosis magnetic resonance imaging (MRI) may be useful. MRI can show inflammation of the sacroiliac joint. Imaging

[C-reactive protein or blood sedimentation reaction os preventive studies in the physician's laboratory?].

The laboratory examinations are more and more significant in the practical internal medicine. The results are basic for decision-making in medicine. The patients are asking for check-up examinations, including screening examinations in the laboratory. We try to compare the significance of two important laboratory tests. The C-reactive protein (CRP) is very sensitive and allows a graduation of the inflammatory reaction. It is useful to take the CRP in a valuable screening examination. Compared with the erythrocyte sedimentation rate (ESR), an elevated CRP always signifies an organic illness. A normal ESR has a poor predictive value. An elevated ESR supports only the history and the clinical findings of a suspected diagnoses. There is no possibility to screen patients without symptoms by ESR. We use ESR to follow-up diseases like arteritis temporalis and polymyalgia rheumatica and to measure the therapeutic effect.

Man with a Swollen Eye: Nonspecific Orbital Inflammation in an Adult in the Emergency Department.

Nonspecific orbital inflammation (NSOI) is a rare idiopathic ocular pathology characterized by unilateral, painful orbital swelling without identifiable infectious or systemic disorders, which can be complicated by optic nerve compromise. A 50-year-old man presented to the Emergency Department with recurring, progressive painless left eye swelling, decreased visual acuity, and binocular diplopia in the absence of trauma, infection, or known malignancy. His physical examination was notable for left-sided decreased visual acuity, an afferent pupillary defect, severe left eye proptosis and chemosis, and restricted extraocular movements; his dilatated funduscopic examination was notable for ipsilateral retinal folds within the macula, concerning for a disruption between the sclera and the retina. Ocular examination of the right eye was unremarkable. Laboratory data were unrevealing. Gadolinium-enhanced magnetic resonance imaging showed marked thickening of the left extraocular muscles associated with proptosis, dense inflammatory infiltration of the orbital fat, and characteristics consistent with perineuritis. The patient was diagnosed with NSOI with optic neuritis and admitted for systemic steroid therapy; he was discharged on hospital day 2 after receiving high-dose intravenous (i.v.) methylprednisolone with significant improvement. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: NSOI is a rare and idiopathic ocular emergency, with clinical mimicry resembling a broad spectrum of systemic diseases such as malignancy, autoimmune diseases, endocrine disorders, and infection. Initial work-up for new-onset ocular proptosis should include comprehensive laboratory testing and gadolinium-enhanced magnetic resonance imaging. Timely evaluation by an ophthalmologist is crucial to assess for optic nerve involvement. Signs of optic nerve compromise include decreased visual acuity, afferent pupillary defect, or decreased color saturation. Patients with optic nerve compromise require admission for aggressive anti-inflammatory therapy with i.v. steroids in an attempt to reduce risk of long-term visual sequelae. Our case demonstrates a severe presentation of this disorder and exhibits remarkable visual recovery after 48 h of systemic i.v. steroid treatment.

InternalMed_Harrison

diagnostic pointers are numerous and diverse but may be missed drug is the cause. In patients without PDCs or with only misleading on initial examination, often being detected only by a very care-PDCs, funduscopy by an ophthalmologist may be useful in the early ful examination performed subsequently. In the absence of PDCs, stage of the diagnostic workup. When the first-stage diagnostic tests the history and physical examination should therefore be repeated do not lead to a diagnosis, scintigraphy should be performed, esperegularly. One of the first steps should be to rule out factitious or cially when the ESR or CRP level is elevated. fraudulent fever, particularly in patients without signs of inflammation in laboratory tests. All medications, including nonprescription Recurrent Fever In patients with recurrent fever, the diagnostic drugs and nutritional supplements, should be discontinued early in workup should consist of thorough history-taking, physical examithe evaluation to

Leber's hereditary optic neuropathy following unilateral painful optic neuritis: a case report.

Leber's hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disease, characterized by acute or subacute, painless, bilateral visual loss. LHON is often misdiagnosed as optic neuritis at an early stage because of the similarity of their clinical presentation. To date, there has been no reported case of actual optic neuritis and LHON in one patient. A 40-year-old, healthy man was referred to our clinic with acute painful visual loss in the right eye for 2 weeks. In the right eye, visual acuity decreased to 20/40, and the Ishihara colour test score was 8/14 with a relative afferent pupillary defect. Optic disc swelling was found only in the right eye, and magnetic resonance imaging revealed enhancement of the the right optic nerve, consistent with optic neuritis. After receiving 1 g of intravenous methylprednisolone daily for three days, his ocular pain resolved, and visual acuity improved to 20/20 within 2 weeks. Seven months later, the patient developed acute painless visual loss in the right eye. Visual acuity decreased to 20/200 in the right eye. There was no response to the intravenous methylprednisolone therapy at that time. Eight months later, he developed subacute painless visual loss in the left eye. Genetic testing for LHON was performed and revealed the pathologic mtDNA 11778 point mutation. We report a case with painful unilateral optic neuritis preceding the onset of LHON. Even if a typical optic neuritis patient has completely recovered from steroid treatment once in the past, it is advisable to keep in mind the possibility of LHON if acute or subacute loss of vision subsequently or simultaneously occurs in both eyes and does not respond to steroids.

Sometimes (what seems to be) a heart attack is (really) a pain in the neck.

A 31-year-old patient complained of severe crushing chest pain that radiated to his left arm and jaw. After admission to the hospital, tests revealed a normal electrocardiogram, normal treadmill, normal coronary arteriogram, and normal cardiac enzymes. However, the patient continued to have pain, which was relieved by sublingual and intravenous nitroglycerine. He was discharged from the hospital with a diagnosis of "musculoskeletal" chest pain, taking nonsteroidal anti-inflammatory drugs, muscle relaxants, and narcotics. Two weeks later, the patient returned with worsening symptoms. Cardiac work-up was again negative. Thoracic and cervical spine radiographs were ordered for possible discogenic pain. After abnormalities were found on cervical radiographs, magnetic resonance imaging (MRI) was ordered, and the patient was referred to an orthopedic surgeon. Further work-up revealed a herniated disk at C6-C7, with radicular pain. Surgery on the suspect disk totally relieved the patient's pain.

Posterior ischemic optic neuropathy

Signs and symptoms PION is characterized by moderate to severe painless vision loss of abrupt onset. One or both eyes may be affected and color vision is typically impaired. Ophthalmoscopic exam Looking inside the person's eyes at the time of onset, ophthalmoscope exam reveals no visible changes to the optic nerve head. Weeks after ischemic insult, nerve atrophy originating from the damaged posterior optic nerve progresses to involve the anterior optic nerve head. Four to eight weeks after onset, atrophy of the optic nerve head is observable upon ophthalmoscope exam. Pupils If both eyes are affected by PION, the pupils may look symmetrical. However, if the eyes are asymmetrically affected, i.e. one eye's optic nerve is more damaged than the other, it will produce an important sign called an afferent pupillary defect. Defective light perception in one eye causes an asymmetrical pupillary constriction reflex called the afferent pupillary defect (APD).

Diagnostic work-up of an elderly patient with unilateral head and neck pain. A case report.

Headache patients frequently contact physiotherapists and manual therapists. In case of elderly patients with unilateral headache, neck and facial pain clinical practice guidelines recommend further referral for medical investigation to exclude red flags. The present patient was seen in a multidisciplinary headache clinic. He was referred by the neurologist (headache specialist) for physiotherapeutic assessment after screening for red flags, including giant cell arteritis (GCA). After first assessment, GCA was considered unlikely, since the sedimentation rate, as a marker for inflammation, was only slightly elevated. The purpose of the referral was to exclude cervicogenic headache (CEH) and to explore physical treatment as a therapeutic option. Physiotherapeutic assessment consisted of a history taking on CEH signs (Sjaastad criteria, 1998), followed by cervical spine assessment including tests for neck mobility, joint pain, and endurance of the short neck flexors. The patient's history revealed no specific signs of CEH and cervical spine assessment was negative. In consultation with the neurologist, the diagnosis of CEH was abandoned. Since palpation of the temporal artery proved to be painful, laboratory examination and biopsy of the temporal artery were thereafter performed, this time revealing GCA. Appropriate treatment (high dose steroids) was initiated promptly, with a good clinical evolution. The presented case shows the potential of a multidisciplinary collaboration in the clinical diagnostic work-up of patients with head and neck pain.

Central retinal artery occlusion as a post-transfusion complication of red blood cells.

A 32-year-old woman presented with a history of uterine myomatosis and repeated bleeding for 6 months. This produced a haemoglobin concentration of 6.5 g/dL, with a requirement for a red blood cell transfusion. One hour after the transfusion, she presented with a sudden and painless loss of vision in the right eye (RE). As she had no other symptoms, she was referred to the Neuro-Ophthalmology Department. On admission, her corrected visual acuity was hand movement in RE, and 0.6 in the left eye (LE). The anterior segment was unremarkable, except for a relative afferent pupillary defect in RE. In the fundus examination, the RE showed a diffuse pale retina with a cherry spot, consistent with occlusion of the central artery of the retina. Management was attempted but with no improvement. The studies corroborated retinal ischaemia in RE. During the systemic evaluation, the neuroimaging, autoimmune and haematology studies were negative, thus this complication was attributed to the red blood cell transfusion.

Headache

One recommended diagnostic approach is as follows. If any urgent red flags are present such as visual loss, new seizures, new weakness, new confusion, further workup with imaging and possibly a lumbar puncture should be done (see red flags section for more details). If the headache is sudden onset (thunderclap headache), a computed tomography test to look for a brain bleed (subarachnoid hemorrhage) should be done. If the CT scan does not show a bleed, a lumbar puncture should be done to look for blood in the CSF, as the CT scan can be falsely negative and subarachnoid hemorrhages can be fatal. If there are signs of infection such as fever, rash, or stiff neck, a lumbar puncture to look for meningitis should be considered. If there is jaw claudication and scalp tenderness in an older person, a temporal artery biopsy to look for temporal arteritis should be performed and immediate treatment should be started. Neuroimaging

Central retinal artery occlusion as initial presentation of Moyamoya disease in a middle-aged woman.

To present a case of central retinal artery occlusion as the first symptomatic manifestation of Moyamoya disease in a middle-aged patient. Case report of a 48-year-old female Chinese-American patient who presented with sudden onset painless unilateral vision loss. Fundus photos, optical coherence tomography, fluorescein angiography, magnetic resonance angiography, computed tomography angiography, and catheter cerebral angiogram were performed. The patient's dilated fundus examination showed classic findings of a central retinal artery occlusion. Diagnostic brain imaging demonstrated extensive stenosis of the cerebrovascular network, with almost complete unilateral occlusion of the internal carotid artery along with compensatory collateral vessels. This led to a new diagnosis of Moyamoya disease. The patient was treated with extracranial-intracranial bypass surgery. Arterial abnormalities in patients with Moyamoya disease are uncommon and have previously only been reported in younger patients in their teens and 20s. Young and middle-aged patients presenting with central retinal artery occlusions should undergo complete neurologic workup including stroke evaluation; in this case, revealing Moyamoya disease, a rare yet life-threatening condition, as the underlying etiology.

Diagnosis of a 65-year-old male patient with Takayasu's arteritis by 18F-FDG PET/CT.

Takayasu's arteritis (TA) is characterized by a chronic inflammatory arteriopathy with unknown etiology affecting large vessels. As TA occurs mostly in young females, elderly males with this disease may be under-diagnosed. A 65-year-old Chinese male with a 6-week history of fever, fatigue, low appetite, night sweats, and a 5-kg weight loss did not experience symptoms of jaw claudication, localized headache, sudden visual change, upper or lower extremity claudication, arthralgia, and rashes. On physical examination and laboratory findings, there was no evidence of infectious disease or malignancy. (18)F-Fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) was performed which suggested TA. The patient was treated with methylprednisolone and clopidogrel. His symptoms subsided gradually and hematological examination showed decreases of erythrocyte sedimentation rate and high-sensitivity C-reactive protein. We reported here a patient who presented with fever of unknown origin and was diagnosed with TA using PET/CT. Although elderly males are beyond the predominant population of TA, TA should be considered when there is no evidence of infectious disease and malignancy.

Ultrasound-guided lumbar puncture

Ultrasound-guided lumbar puncture is a medical procedure used in some emergency departments to obtain cerebrospinal fluid for diagnostic purposes. In contrast to standard lumbar puncture by palpation, the use of ultrasound imaging may reduce the number of failed punctures, needle insertions, and needle redirections. Ultrasound-guided lumbar puncture was first described in Russian medical literature in 1971. References CSF tests Medical ultrasonography Neurology procedures

Progression of preexisting trigeminalgia to Tolose-Hunt-like syndrome. The importance of neuroimaging for early differential diagnosis.

Recurrent unbearable, paroxysmal, unilateral facial pain in the distribution of one or more branches of the trigeminal nerve often provoked by sensory stimuli is typical for idiopathic trigeminal neuralgia. The less frequent localization in the area of ophthalmic branch (5%) is particularly controversial and should be distinguished from pathological lesions in the brainstem and middle and posterior cranial fossa and from diseases of the orbit and eye. This case study presents a 79-year-old woman with typical clinical features of 1st division trigeminalgia without any neurological loss and with normal results of laryngological, ophthalmological, and stomatological examinations as well as neuroimaging CT, and MR /MRA evaluation. Only the evoked potential blink and masseter reflexes demonstrated the pathological values in the early phase of illness. After 1 year of pharmacological treatment no improvement was achieved and the pain became neuropathic and paresis of 3rd, 4th and 6th nerves developed, as observed in Tolose-Hunt syndrome. MRI of the orbit revealed a pathological mass in its apex with a connection to the superior orbital fissure. However, treatment with steroids was completely ineffective. Surgical resection of the tumor (leiomyosarcoma) only partially reversed oculomotor palsy and diminished aching. In differential diagnosis of idiopathic and symptomatic trigeminalgia, early MR and MRA imaging is the most essential and sometimes may be the best single test to evaluate lesions even in distant areas of the nervous system branches.