The other tests can wait...

The other tests can wait...

The other tests can wait...

The other tests can wait...

The clinical and biological picture of this patient raises suspicion of hemolytic anemia in the context of systemic lupus erythematosus. If we have to choose only one diagnostic test, and this should be the first, we are interested in confirming the presence of an autoimmune hemolytic anemia with the direct Coombs' test in order to initiate treatment. The other tests can wait...

A 25-year-old female patient with a history of skin rash after sun exposure and occasional polyarthritis in the joints of the hands, controlled with non-steroidal anti-inflammatory drugs, presents with general malaise, progressive feeling of generalized weakness and pallor for the last 15 days. Laboratory tests showed hemoglobin 7 g/dL, MCV 108 mm/h, 150,000 platelets/mm3, 3000 leukocytes/mm3, elevated LDH, undetectable haptoglobin. In the case of choosing a single diagnostic test indicate which of the following determinations should be performed first:

[An elderly case of systemic lupus erythematosus associated with herpes zoster, anemia, and hemiparesis].

An elderly case of systemic lupus erythematosus (SLE) with suspected hemolytic anemia was experienced. A 70 year-old female was admitted to our hospital on December 31 with complaints of herpetic eruption. She complained of arthralgia since 3 month prior to her admission. The positive findings on examination were skin eruption in the left chest, a systolic heart murmur and a palpable elastic hard liver. Laboratory data showed raised erythrocyte sedimentation rate of 149 mm per hour, decreased Hb (10.1 g/dl), decreased hematocrit (30.0%), increased reticulocytes (33%1000), decreased thrombocytes (73,000/mm3), increased gamma-globulin (33%) and positive rheumatoid factor. During admission, she developed anemia. A stool test for occult blood was negative. The haptoglobin was 38.8 mg/dl and bone marrow aspiration showed increased erythropoiesis, suggesting features of immune hemolytic anemia, except she was negative on Coomb'test. Eye fundi were similar to case of typical bleeding observed in SLE. Concerning immunological findings, the antinuclear factor was x 1280 and the anti-dsDNA antibody was x 80, on which a diagnosis of SLE was based. She experienced numbness of the left arm and developed left hemiparesis 2 days later. Therapy with 15 mg/day prednisone obtained a good response and anemia, abnormal immunological findings and hemiparesis disappeared.

Late-Onset Systemic Lupus Erythematosus Associated with Autoimmune Hemolytic Anemia and Sixth Cranial Nerve Palsy.

BACKGROUND Patients with late-onset systemic lupus erythematosus (SLE) do not present with typical SLE symptoms or serology, and this can lead to a major delay in diagnosis. We report a complex case of an older woman who developed autoimmune hemolytic anemia and sixth cranial nerve palsy that posed considerable challenges in diagnosing late-onset SLE. CASE REPORT A 78-year-old Japanese woman presented with polyarthritis associated with generalized fatigue for 2 months, who later developed diplopia. Physical examination revealed conjunctival pallor, polyarthritis, and subsequent development of sixth cranial nerve palsy. Laboratory data revealed a decreased white blood cell count; macrocytic anemia; elevated levels of lactate dehydrogenase, indirect bilirubin, and erythrocyte sedimentation rate; hypocomplementemia; positive Coombs test; antinuclear antibodies (ANAs, 1: 40); and positive anti-double-strand DNA antibodies. Lymphoma, cerebral venous sinus thrombosis, and varicella-zoster virus infection were unlikely based on head computed tomography, brain magnetic resonance imaging, and cerebrospinal fluid analysis. She was diagnosed with late-onset SLE associated with autoimmune hemolytic anemia and sixth cranial nerve palsy. The patient was successfully treated with prednisone and hydroxychloroquine. CONCLUSIONS The difficulty in diagnosing late-onset SLE with atypical presentations and uncommon complications must be recognized. SLE cannot be excluded based on a low titer of ANA in a particular subgroup such as the elderly, and the prozone effect should be considered responsible for low ANA titers. In this case, late-onset SLE was diagnosed by considering multisystem pathologies despite low ANA titers.

InternalMed_Harrison

Fever >38.3°C (101°F) on at least two occasions 2. Illness duration of ≥3 weeks 3. 4. Diagnosis that remains uncertain after a thorough history-taking, physical examination, and the following obligatory investigations: determination of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level; platelet count; leukocyte count and differential; measurement of levels of hemoglobin, electrolytes, creatinine, total protein, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, creatine kinase, ferritin, antinuclear antibodies, and rheumatoid factor; protein electrophoresis; urinalysis; blood cultures (n = 3); urine culture; chest x-ray; abdominal ultrasonography; and tuberculin skin test (TST). The range of FUO etiologies has evolved over time as a result of changes in the spectrum of diseases causing FUO, the widespread Percentage of Cases Due to Indicated Cause

Case 291.

History A 46-year-old woman with known mixed connective tissue disease with clinical features of scleroderma and polymyositis and who was not on specific medications was referred to our institution to assess for interstitial lung disease due to her predisposing condition. She was a nonsmoker, had no respiratory symptoms, and enjoyed good exercise tolerance. She did not have any cutaneous lesions or renal disease. There was no family history of pulmonary or systemic disease. Her routine blood test results revealed a white blood cell count of 4.6 × 10<sup9</sup/L (normal range, [4.4-10.1] × 10<sup9</sup/L), a hemoglobin level of 7.76 mmol/L (normal range, 7.26-9.18 mmol/L), a platelet count of 189 × 10<sup9</sup/L (normal range, [170-380] × 10<sup9</sup/L), a bilirubin level of 8 μmol/L (7-19 μmol/L), and a creatinine level of 63 μmol/L (45-82 μmol/L), all within normal limits. Lung function tests at presentation yielded normal results, with a diffusing capacity for carbon monoxide of 95% and a forced vital capacity of 2.29 (98% predicted value). However, this patient had an elevated serum globulin level of 47 g/L (normal range, 26-32 g/L) and an erythrocyte sedimentation rate of 36 mm/h (normal range, 0-20 mm/h), while C-reactive protein level was normal at less than 0.35 mg/dL. She was seropositive for antinuclear (titer >1/720), anti-Ro, anti-La, and anti-extractable nuclear antigen antibodies. Chest radiography and CT were performed at presentation (Figs 1, 2) and 14-year follow-up (Figs 3, 4). PET/CT was performed at 7- (Fig 5, <iA</i and <iB</i) and 13-year follow-up (Fig 5, <iC</i and <iD</i). Throughout this 14-year follow-up period, she remained completely free of respiratory symptoms and continued to go for a brisk walk every day. At 14-year follow-up, there was no substantial change in serum laboratory values, but a lung function test revealed her diffusing capacity for carbon monoxide had decreased to 52%, while her forced vital capacity remained good at 95%; these findings were suggestive of interval development of restrictive lung function.

InternalMed_Harrison

Fever ˜38.3° C (101° F) and illness lasting ˜3 weeks and no known immunocompromised state History and physical examination Stop antibiotic treatment and glucocorticoids Obligatory investigations: ESR and CRP, hemoglobin, platelet count, leukocyte count and differential, electrolytes, creatinine, total protein, protein electrophoresis, alkaline phosphatase, AST, ALT, LDH, creatine kinase, antinuclear antibodies, rheumatoid factor, urinalysis, blood cultures (n=3), urine culture, chest x-ray, abdominal ultrasonography, and tuberculin skin test

Severe hemolysis with negative direct antiglobulin test: A case report.

A 49-year-old woman with type 2 diabetes mellitus (T2DM) presented to the emergency department. Her examination showed marked pallor, exhaustion, lethargy, yellowish eyes, anorexia, nausea and vomiting. Hematuria; negative standard direct antiglobulin test (DAT); normal glucose 6 phosphate dehydrogenase (G6PD); hemoglobin (Hb), 4.8 g/dl; Mean cell volume (MCV), 91fl; platelet count, 233 × 10<sup6</sup/L; Total bilirubin, 7.0 mg/dl; Glucose, 316 mg/dl; lactate dehydrogenase (LDH), 1750U/L. Undoubtedly, therapeutic panel should have been used for hemolytic anemia. Intravenous (IV) fluids and 2 units of packed cell were transfused. Methylprednisolone with rituximab were started for the patient. After 3 weeks of the patient admission, she was discharged home with stable vital signs and Hb, 10 g/dl. We concluded in the cases that presented along with a severe drop in Hb and evidence of hemolysis which non immune hemolytic anemia is excluded in spite of negative standard DAT limited transfusion besides corticosteroids combined with rituximab, could be helpful in saving the patient.

Rheumatoid arthritis

The by far most common clinical test for ACPAs is the anti-cyclic citrullinated peptide (anti CCP) ELISA. In 2008 a serological point-of-care test for the early detection of RA combined the detection of RF and anti-MCV with a sensitivity of 72% and specificity of 99.7%. Other blood tests are usually done to differentiate from other causes of arthritis, like the erythrocyte sedimentation rate (ESR), C-reactive protein, full blood count, kidney function, liver enzymes and other immunological tests (e.g., antinuclear antibody/ANA) are all performed at this stage. Elevated ferritin levels can reveal hemochromatosis, a mimic of RA, or be a sign of Still's disease, a seronegative, usually juvenile, variant of rheumatoid arthritis. Classification criteria In 2010, the 2010 ACR / EULAR Rheumatoid Arthritis Classification Criteria were introduced.

Severe Vitamin B12 Deficiency Presenting as Pancytopenia, Hemolytic Anemia, and Paresthesia: Could Your B12 Be Any Lower?

Although severe vitamin B12 deficiency is rare in the United States, recent increases in the adoption of vegan lifestyles have led to a significant rise in the rates of B12 deficiency, along with its hematologic and neurologic sequelae, the latter of which is often irreversible. We describe a case of a 39-year-old male who presented with a several-month history of progressively worsening word-finding difficulties, shortness of breath, and a four-day history of bilateral hand numbness and tingling. Laboratory data revealed pancytopenia with profound anemia. Markers of hemolysis were positive, including elevated indirect bilirubin, disproportionately elevated lactate dehydrogenase (LDH), low haptoglobin, negative direct anticoagulant test, and hypoproliferative reticulocyte index. Blood smear revealed hypersegmented neutrophils and macrocytosis. Vitamin B12 levels were undetectable, and anti-intrinsic factor and parietal cell antibodies were negative. A thorough history revealed a 20-year history of strict veganism without B12 supplementation. He was transfused with packed red blood cells and started on subcutaneous B12 injections with rapid improvement of his symptoms. Early recognition of B12 deficiency causing the constellation of pancytopenia, hemolytic anemia, and neurologic symptoms is vital in preventing irreversible neurologic sequelae. This case also highlights the importance of accurate history taking to aid in early diagnosis of B12 deficiency, especially in the context of rising rates of veganism in the United States.

[A case of elderly-onset systemic lupus erythematosus (SLE) complicated with severe liver dysfunction and pancytopenia due to myelofibrosis].

A 67-year-old woman was admitted to our hospital with a fever. She had been experiencing arthralgia for about one month. On admission, she had a fever of 38.5 degrees C, was anemic and was experiencing tenderness in the joints of both hands, elbows and feet. Laboratory data revealed proteinuria, urinary cylinders, pancytopenia (WBC 900/mm3, Hb 9.5 g/dl, Plt 7.8 x 10(4)/mm3), liver dysfunction (GOT 414 IU/l, GPT 140 IU/l), and hyper-gamma globulinemia. Antibiotics and granulocyte-colony stimulating factor were administered intravenously. Bone marrow aspiration was unsuccessful, but a bone marrow biopsy revealed bone marrow fibrosis. Immunological examinations were positive for antinuclear antibodies, anti-deoxyribonucleic acid (DNA) antibodies, anti-double stranded anti- DNA antibodies, as well as a decreased level of serum complement and an increased level of serum immune complexes. Tests for viral antigens and antibodies known to cause hepatitis were negative. Based on these findings, a diagnosis of SLE accompanied by liver dysfunction and bone marrow fibrosis was made. Steroid pulse therapy was initiated, but her liver function deteriorated on the first day of steroid therapy, and she died three days later. SLE accompanied by myelofibrosis is extremely rare, and only 17 and cases have been reported to date. Among these reports, the present case is the second oldest subject and the first SLE patient to suffer from both myelofibrosis and severe liver dysfunction.

Adult-onset Still's disease: a report of 28 cases and review of the literature.

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology. It is characterized by fever, skin rash, polyarthralgias or polyarthritis, sore throat, hepatosplenomegaly, lymphadenopathy, leukocytosis, liver enzyme elevation, and high serum level of ferritin. Several kinds of skin lesions have been reported in this condition. The aim of this study was to assess the clinical and laboratory aspects of 28 patients with AOSD in central Iran. According to the diagnostic criteria of AOSD, we identified 28 patients between 2002 and 2007. We intended to describe the clinical characteristics, treatment, and outcome of our patients with AOSD. Of 28 patients with AOSD, 21 (75%) were female, 7 (25%) were male. Fever (100%), sore throat (92%), Arthralgia (92%), dermatographism (92%), typical rash (85%) and arthritis (60%) were the most common findings. The mean values of laboratory findings were as follows; C-reactive protein (CRP) level of 14.4 mg/dl, erythrocyte sedimentation rate (ESR) of 91.5 mm/h, leukocyte count of 15744.4/microl. Abnormal levels of aspartate aminotransferase and alanine aminotransferase were observed in 25 (89%) patients. Twenty patients (71%) had high ferritin values (>500 ng/ml). The clinical characteristics were similar to previous series. A febrile polyarthritis was the most frequent presentation form. Dermatographism was frequently encountered phenomenon in our patients with AOSD. Being that dermatographism is a simple inducible skin reaction, along with its sensitivity in active disease, we suggest more controlled studies to validate accuracy and positive predictive value of it in convenient clinical setting in the diagnosis of AOSD and to consider including it in diagnostic criteria.

Autoimmune hemolytic anemia

Laboratory investigations are carried out to determine the etiology of the disease. Following confirmation of hemolysis (seen with laboratory markers of low hemoglobin, elevated LDH, decreased haptoglobin, and elevated unconjugated bilirubin), a direct antiglobulin test (DAT)(also known as a Coomb's test) is done to show auto-immune pathogenesis with antibodies, compliment or both on the erythrocyte surface. This is followed by a monospecific DAT that identifies the specific antibody and compliment types on the erythrocyte surface. In cold agglutinin disease, the monospecific DAT is by definition positive for the compliment molecule C3d but IgM may be negative as the molecule may detach at the time of testing. The diagnosis of cold agglutinin disease is confirmed with an elevated cold agglutinin titer. A bone marrow biopsy is used in AIHA to identify a possible underlying lymphoproliferative disorder.

Viral Arthritis -- Evaluation -- Diagnosis

There is no single test or clinical presentation which is suggestive of viral arthritis. The diagnosis is mainly clinical, supported by other tests, including inflammatory markers, autoantibodies, and serology. A viral etiology should be suspected in a patient presenting with acute onset of arthralgias or polyarticular symptoms, especially if the duration of symptomatology has been less than six weeks. The presence of extra-articular symptoms, viz rash or lymphadenopathy, should be noted. Testing for antinuclear antibodies (ANA), rheumatoid factor (RF), and anti-citrullinated protein antibodies (ACPA) could be helpful if the features of inflammatory arthritis persist. In suspected cases of viral arthritis, the serum should be collected for serology. Serologic testing, however, must be directed against the specific viruses suspected based upon both epidemiologic and clinical data. As a general rule with serology, an IgM antibody response would be indicative of acute infection and would be converted to an IgG isotype after a few weeks. Due to the high rate of infections in the general population, for example, with EBV and hepatitis, positive IgG antibodies, especially if stable in titers, are non-diagnostic. Other laboratory features are related to the specific viral syndromes. For example, the detection of positive HBsAg elevated aminotransferases and IgM anti-HBc antibodies in a patient with recent-onset polyarthritis could provide the clue to the diagnosis of HBV-associated polyarthritis. Isolation of virus from the joint itself or viral cultures is not useful except in rare circumstances.

[Acute cardiac failure due to dilated cardiomyopathy in systemic lupus erythematosus with antiphospholipid antibody].

A 33-year-old man presented malar rash in April, 1992. The rash had gradually developed and he was admitted to our hospital in February, 1994. Laboratory findings showed proteinuria of 0.5-0.8 g/ day, thrombocytopenia (4.8 x 10(4)/mm3), false positive serologic test for syphilis, anti-nuclear antibody with a speckled type at a titer of 1 : 80. Activated partial thromboplastin time was prolonged (41.3 s), and anti-beta 2-GPI antibody was strongly positive (56.6 U/ml on enzyme linked immunosorbent assay). The diagnosis of systemic lupus erythematosus with antiphospholipid syndrome was made and prednisolone 60 mg/day improved his manifestations. He could be discharged in July, 1994. Nine months after the discharge he developed dyspnea, and he was admitted to our hospital again. On admission the blood pressure was 212/170 mmHg, Levine III/VI systolic murmur was noted at the apex of heart. Significant laboratory findings showed as follows: WBC 15, 110/mm3 (Neu 73%, Lym 18%), RBC 380 x 10(4)/mm3, Hb 10.2 g/dl, Plt 20.0 x 10(4)/mm3, GOT 23 IU/l, GPT 21.

Paroxysmal nocturnal hemoglobinuria

Diagnosis Blood tests in PNH show changes consistent with intravascular hemolytic anemia: low hemoglobin, raised lactate dehydrogenase, raised bilirubin (a breakdown product of hemoglobin), and decreased levels of haptoglobin; there can be raised reticulocytes (immature red cells released by the bone marrow to replace the destroyed cells) if there is no iron deficiency present. The direct antiglobulin test (DAT, or direct Coombs' test) is negative, as the hemolysis of PNH is not caused by antibodies. If the PNH occurs in the setting of known (or suspected) aplastic anemia, abnormal white blood cell counts and decreased platelet counts may be seen at this. In this case, anemia may be caused by insufficient red blood cell production in addition to the hemolysis.

[Meningococcemia: Different Serotypes in the Same Region].

Meningococcal infections are important health problems causing high morbidity and mortality. Neisseria meningitidis have 13 serogroups. A, B, C, Y and W135 are the most common causes of invasive disease among those serogroups. The distribution of the serogroups differs according to the geographical regions and the age groups. In this case report, two cases of meningococcemia infected with serogroup C and Y of N.meningitidis rarely seen in our country were presented. First case was a two and a half year-old female patient who has admitted to our pediatric emergency unit with fever and rash spreading from lower extremities to her body. The patient had diffuse purpuric rash with generalized weakness and tendency to sleep at admission. The patient has been suspected as meningococcemia because of the skin rash, tendency to sleep and hypotension. Antibiotics treatment was started immediately and lumber puncture was performed. In blood tests, leukocyte count: 3600/mm3 (61% neutrophils), hemoglobin: 11.1 g/ dl, platelet count: 127.000/mm3 , C-reactive protein: 10 mg/dl, erythrocyte sedimentation rate: 6 mm/ hour, prothrombin time: 28.8 seconds (normal value= 11-16), prothrombin activity: 36%, international normalized ratio (INR): 2.13 (normal value= 1-1.5), activated partial thromboplastin time: 57.7 seconds (normal value= 25-35 sec), fibrinogen: 246 mg/dl (normal value= 200-400 mg/dl) and in cerebrospinal fluid protein: 21 mg/dl and glucose: 62 mg/dl were found. There were eight cells in the microscopic examination. Skin rashes were increased and the patient became hypotensive. No microorganisms were isolated in blood and cerebrospinal cultures. N.meningitidis serogroup C was isolated from the cerebrospinal fluid of the patient using polymerase chain reaction (PCR). The patient suffered from immune-mediated arthritis in the sixth day of treatment and nonsteroidal anti-inflammatory drugs were given. The patient has recovered with antibiotics, fresh frozen plasma and inotropic treatment. Second case was a 13 year-old male patient who has admitted three days after the first case with a pre-diagnosis of malignancy because of pancytopenia and fever. The patient had generalized weakness and a few petechial purpuric rashes at the facial region at admission. After the admission general status of the patient has worsened rapidly and he has died as a result of cardiovascular arrest. Blood tests in admission showed leukocyte count: 6000/mm3 (79% neutrophils), hemoglobin: 17.3 mg/dl, platelet count: 16.000/mm3 , C-reactive protein: 8.63 mg/dl, prothrombin time: 92.6 seconds, prothrombin activity: 10%, INR: 6.78, activated partial thromboplastin time: 231.5 seconds. Cerebrospinal fluid obtained from postmortem lumbar puncture showed no growth (protein: 95 mg/dl, glucose: 35 mg/dl) and N.meningitidis serogroup Y was detected by PCR. Two meningococcemia cases caused by two different serogroups which are rarely seen in our region in recent years were presented at the same time period in the same hospital. This case report pointed out that surveillance has a great importance in such diseases.

A puzzle of hemolytic anemia, iron and vitamin B12 deficiencies in a 52-year-old male.

A 52-year-old male with no significant past medical history reports increasing generalized fatigue and weakness for the past 2 weeks. Physical examination reveals jaundice and pallor without organomegaly or lymphadenopathy. His hemoglobin was 5.9 g/dL with a mean corpuscular volume of 87.1 fL and elevated red blood cell distribution width of 30.7%. His liver function test was normal except for elevated total bilirubin of 3.7 mg/dL. Serum LDH was 701 IU/L, and serum haptoglobin was undetectable. Further investigation revealed serum vitamin B12 of <30 pg/mL with elevated methylmalonic acid and homocysteine level. In addition, serum ferritin and transferrin saturation were low. The patient was diagnosed with hemolytic anemia secondary to vitamin B12 deficiency with concomitant iron deficiency anemia.

[Autoimmune hemolytic anemia with eosinophilia in elderly patient].

A 70-year-old woman was admitted to our hospital in November 1992 for evaluation of anemia. Physical examination revealed anemia, jaundice, swelling of axial and inguinal lymph nodes, and splenomegaly. Abnormal hematological findings were as follows: Hb of 3.9 g/dl, reticulocyte count of 58.2% (61.7 x 10(4)/microliters), hyperplasia of normal erythroblasts in bone marrow, and eosinophilia (21.0%, 2352/microliters) in peripheral blood. Routine laboratory examinations revealed polycolonal hypergammaglobulinemia 3.0 g/dl, a high level of serum LDH (797 IU/I) and a total bilirubin of 2.4 mg/dl (indirect, 1.6 mg/dl). The serum haptoglobin level was very low (< 5 mg/dl). Results of serological examinations were as follows: IgG of 3366 mg/dl, CH50 of 16.0 U/ml, positive Coombs test 2+, and positive tests for antinuclear antibody, rheumatoid factor, and cold agglutinin. CRP was negative. PHA-stimulated lymphocyte blast formation, NK activity, and ADCC activity were found to be suppressed, and the percentage of CD4-positive lymphocytes in peripheral blood was also low. An axillary lymph node biopsy revealed reactive lymphadenitis. No signs or history suggested allergy, collagen disease, or parasitic infection. Autoimmune hemolytic anemia (AIHA) complicated by immunologic abnormalities and eosinophilia was diagnosed. Oral prednisolone markedly reduced the hemolytic anemia, eosinophilia, lymph node swelling, and splenomegaly, but NK activity remained low.

[A Case of Simultaneous Acute Lymphoblastic Leukemia Diagnosis with Crimean-Congo Hemorrhagic Fever].

Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease that can be presented with fever, fatigue, generalized joint/body pain, diarrhea and bleeding in various parts of the body. The risk of developing a severe fatal disease in humans, the possibility of being infected with aerosols and the risk of being used as a biological weapon make the disease still an important health problem all over the world as there is no a specific treatment and vaccine that has proven effective againt the virus today. The pathogenesis of the disease is not known, but vascular endothelial damage is prominent. Therefore, it progresses with thrombocytopenia, anemia, leukopenia and this hematological findings can be confused with hematological malignancies. Acute lymphoblastic leukemia (ALL) is a malignancy included in differential diagnoses and occurs as a result of mutations occuring at a stage of differentiation in the lymphoid precursor cells in the bone marrow. In this study, we present a case of ALL who was diagnosed with CCHF simultaneously. A 43-year old female patient who works in the library and does not have a chronic disease other than asthma and thyroid disorder, has admitted to our hospital with the complaints of intermittent fever, weakness, generalized joint and body pain for about 3 weeks. She had fever and the physical examination revealed bilateral cervical and right postauricular lymphadenopathies. Her aspartate aminotransferase: 77 U/L, alanine aminotransferase: 117 U/L, lactate dehydrogenase: 616 U/L, hemoglobin: 8.27 g/dl, leukocyte count: 15.690/mm3 , neutrophil count: 550/mm3 (%3.5), lymphocyte count: 6690/mm3 (%42.6), platelet count: 102.100/mm3 , C-reactive protein: 163.6 mg/L was detected and the patient was hospitalized on 5 August 2019 for further examination and treatment. Considering that the patient may have viral infection in the foreground the requested test results were detected as; anti-CMV IgM negative, anti-CMV IgG positive, anti-toxoplasma IgM negative, anti-toxoplasma IgG positive, anti-rubella IgM negative, anti-rubella IgG positive, HBsAg negative, anti-HBc IgM negative, antiHBs positive, anti-HAV IgM negative, anti-HAV IgG positive, anti-HCV negative, anti-HIV negative, EpsteinBarr virus (EBV) VCA IgM negative, EBV VCA IgG positive, EBV EBNA IgG positive. Brucella Rose Bengal and Coombs tube agglutination was found be negative. As the cytopenia of the patient deepened, the patient was accepted to have neutropenic fever and it was planned to start piperacillin-tazobactam 4 x 4.5 g/day and two units of erythrocyte replacement therapy. When the patient's history was questioned again, it was learned that she had a tick on her neck about three weeks ago and she had removed the tick herself; 4-5 days later she had the complaints of fever and flu like symptoms and also diarrhea complaints lasting for 3-4 days. Considering the current anamnesis and laboratory findings, the patient was thought to have CCHF and the patient was isolated. The serum sample taken from patient with an initial diagnosis of CCHF and sent to Department of Microbiology Reference Laboratory Public Health Agency of Turkey. The patient was referred to the Antalya Training and Research Hospital. The patient's CCHF serum result was positive. Ribavirin treatment was not initiated in the patient who was accepted to be in the convalescence period, piperacillin-tazobactam 4 x 4.5 g/day treatment was continued and supportive treatment was given. In the follow-up, as the patient's neutropenia, thrombocytopenia and lymphocytopenia still continuing, she was transferred to hematology clinic for malignancy examination and bone marrow biopsy performed by hematology and B cell ALL was diagnosed. She was accepted to be convalescent in terms of CCHF and chemotherapy was started for ALL treatment by hematology. The patient is still being followed up by the hematology clinic and allogenic hematopoietic stem cell tranplantation is planned for the patient. As a result, CCHF is a disease that can be confused with many differential diagnosis. With this case, it is aimed to draw attention to the diagnostic difficulties of CCHF and ALL and to be the first case in the literature.

Pancytopenia associated with 5-aminosalicylic acid use in a patient with Crohn's disease.

We report a case of pancytopenia in a 23-year-old man with Crohn's disease who was treated with 5-aminosalicylic acid (Pentasa; Nisshin, Tokyo, Japan) 3.0 g/day. He developed fever, nausea, diarrhea, and malaise and stopped taking on the third day after commencing Pentasa. Ten days after withdrawal of Pentasa, he was admitted to hospital because of worsening symptoms. Hematologic evaluation disclosed pancytopenia: red blood cells 283 x 10(4)/mm3; white blood cells 700/mm3; and platelets 8000/mm3. Other pertinent laboratory data, including liver and renal function tests results, serology for virus infection, and serum levels of vitamin B12 and folic acids, were normal. Bone marrow examination showed a generalized hypocellular picture, suggestive of drug-induced bone marrow suppression. He received blood transfusion and recombinant human granulocyte colong-stimulating factor (filgrastim). The leucopenia and thrombocytopenia resolved on the 7th and 13th days of hospitalization, respectively. The anemia continued because of bloody stool caused by Crohn's disease. However, reticulocytes were markedly increased in number on the 13th day of hospitalization. He is well at 9 months follow-up. Excluding other causes, Pentasa-associated pancytopenia was considered. The increasing use of this agent is expected, because of the increasing number of patients with inflammatory bowel disease. Careful clinical and hematological monitoring should be performed, especially for the first 3 months, in patients beginning treatment with Pentasa. The drug should be withdrawn immediately if there is a suspicion of blood disorders.

[A case of autoimmune lymphoproliferactive syndrome and literature review].

To summarize the clinical characteristics, diagnosis and treatment of a case with autoimmune lymphoproliferative syndrome (ALPS) . The patient was diagnosed as autoimmune lymphoproliferactive syndrome (ALPS) after being admitted to the Department of Rheumatism and Immunology of Tianjin Children's Hospital in February 20, 2014. The clinical characteristics, physical examination, laboratory tests, gene tests, and treatment process were analyzed and related literature was reviewed. The patient was a 16-month- old boy.Since the first month of life, he started to have repeatedly fever, diarrhea, shortness of breath, lymphadenopathy, hepatosplenomegaly, anemia (HGBmin 50 g/L) and thrombocytopenia (min 35 × 10⁹/L) . But multiple exams showed a normal peripheral blood leukocyte count, hypergammaglobulinemia (IgG 19 800 mg/L, IgA 1 710 mg/L, IgM 2 590 mg/L) and significantly increased serum vitamin B12. Flow cytometric measures showed that CD3⁺ CD4⁻ CD8⁻ T lymphocytes significantly increased ( > 10%) at four times. The count of CD3⁺ TCRαβ⁺ CD4⁻ CD8⁻T lymphocytes (double negative T cells; DNTs) >3% twice. The genetic test showed that 309th FAS gene area showed heterozygous mutations, the boy was diagnosed as ALPS. Added examinations of lymphocytes apoptosis induced by FAS was positive. He was treated with prednisone 15 mg once daily and immunomodulator 150 mg three times a day, while in maintaining period with normal levels of hemoglobin and platelet, the dose of prednisone was reduced gradually. Till now, the patient has been treated and observed for 8 months. We retrieved the reports of ALPS in the databases at home and abroad published in recent 10 years, more than 400 cases reported from foreign countries, but there were only 5 domestic cases. Among those, 4 had onset in infancy and 1 at 6-years of age. All the cases presented servere lymphadenopathy and hepatosplenomegaly with anemia (4 of them with hemolytic anemia) and thrombocytopenia. Three cases had a history of frequent infection, one of them had glomerulonephritis. All patient with significant high level of serum immunoglobulin ( > 1.5 times upper limit of normal range), in 3 of them serum vitamin B12 was > 1.5 pg/L (the other 2 cases missed the exam). In 5 cases CD3⁺ CD4⁻ CD8⁻T cells > 10%, and in 2 case DNTs were 8.9% and 15.7% respectively (the other 3 cases missed the exam). Three cases were clearly detected with FAS mutations. All patients were treated with corticosteroid, 2 of them were added with mycophenolate mofetil. The therapy presented effective result in early 1-3 months, but no long-term follow-up reports were available. ALPS is a disorder of disrupted lymphocyte homeostasis caused by defective Fas-mediated apoptosis, and it is one of the primary immunodeficiency diseases. The onset of the disease occurs during infancy mainly. Clinical lymphoid hyperplasia and autoimmune phenomena are outstanding signs, which can be associated with frequent infections and allergies. The level of serum vitamin B12 > 1.5 pg/L and the count of CD3⁺ CD4⁻ CD8⁻ T cell show important significance. Exact diagnosis should depend on detecting DNTs and FAS gene.

Klinefelter's syndrome presenting with leg ulcers.

A 54-year-old man of Persian origin presented to our department with a 1-year history of ulcers on the right leg that had been unresponsive to numerous topical treatments, accompanied by lymphedema of the right leg. Medical history included hypergonadotropic hypogonadism, which had not been further investigated. He was treated for 20 years with testosterone IM once monthly, which he stopped a year before the current hospitalization for unclear reasons. The patient reported no congenital lymphedema. Physical examination revealed two deep skin ulcers (Figure 1) on the right leg measuring 10 cm in diameter with raised irregular inflammatory borders and a boggy, necrotic base discharging a purulent hemorrhagic exudate. Bilateral leg pitting edema and right lymphangitis with lymphadenitis were noted. He had low head hair implantment, sparse hair on the body and head, hyperpigmentation on both legs, onychodystrophia of the toenails (mainly the large toe and less prominent on the other toes), which was atrophic lichen-planus-like in appearance and needed no trimming (Figure 2), normal hand nails, oral thrush, and angular cheilitis. Other physical findings were gynecomastia, pectus excavatum, small and firm testicles, long extremities, asymmetrical goiter, systolic murmur 2/6 in left sternal border, and slow and inappropriate behavior. The patient's temperature on admission was 39 degrees C. Blood cultures were negative for bacterial growth. Results of laboratory investigations included hemoglobin (11.2 g/dL), hematocrit (26.8%), normal mean corpuscular volume and mean corpuscular hemoglobin volume, and red blood cell distribution width (16%). Blood smear showed spherocytes, slight hypochromia, anisocytosis, macrocytosis, and microcytosis. Blood chemistry values were taken for iron (4 micro g/dL [normal range 40-150 micro g/dL]), transferrin (193 mg/dL [normal range 220-400 mg/dL]), ferritin (1128 ng/mL [normal range 14-160 ng/mL]), transferrin saturation (1.5% [normal range 20%-55%]), serum folate (within normal limits), and vitamin B12 (within normal limits). Direct Coombs' test equaled positive 2 + IgG. All these values indicated anemia of chronic diseases combined with hemolytic anemia. Further blood work-up tested antinuclear antibody (positive <1:80 homogeneous pattern), rheumatoid factors (143 IU/mL [positive >8.5 IU/mL]), C-reactive protein (286 mg/L [normal range 0-5 mg/L]), anticardiolipin IgM antibody (9.0 monophosphoryl lipid U/mL [normal range 0-7.00 MPL U/mL]) and antithrombin III activity (135% [normal range 74%-114%]). Results of other blood tests were within normal limits or negative, including lupus anticoagulant, beta2 glycoprotein, anticardiolipin IgG Ab, anti-ss DNA Ab, C3, C4, anti-RO, anti-LA, anti-SC-70, anti-SM Ab, P-ANCA, C-ANCA, TSH, FT4, anti-T microsomal, antithyroglobulin, protein C activity, protein S free, cryoglobulins, serum immunoelectrophoresis, VDRL, hepatitis C antibodies, hepatitis B antigen, and human immunodeficiency virus. Endocrinological work-up examined luteinizing hormone (22.9 mIU/mL [normal range for adult men 0.8-6 mIU/mL]), follicle stimulating hormone (49.7 mIU/mL [normal range for adult men 1-11 mIU/mL]), testosterone (0.24 ng/mL [normal range for adult men 2.5-8.0 ng/mL]), bioavailable testosterone (0.02 ng/mL [normal range for adult men >0.6 ng/mL]), and percent bioavailable test (8.1% [normal value >20%]). These results indicate hypergonadotropic hypogonadism. Plasminogen activator inhibitor 1 was 6 U (normal value 5-20 U/mL). Karyotyping performed by G-banding technique revealed a 47 XXY karyotype, which is diagnostic of Klinefelter's syndrome. Doppler ultrasound of the leg ulcers disclosed partial thrombus in the distal right femoral vein. X-rays and bone scan displayed osteomyelitis along the right tibia. Histological examination of a 4-mm punch biopsy from the ulcer border revealed hyperkeratosis, acanthosis, hypergranulosis, and mixed inflammatory infiltrate containing eosinophils compatible with chronic ulcer. Multiple vessels were seen, compatible with a healing process. Direct immunofluorescence of the biopsy revealed granular IgM in the dermo-epidermal junction. Indirect immunofluorescence was negative. Thyroid function tests showed normal thyroid stimulating hormone and free throxine4. Multinodular goiter was seen on thyroid scan and ultrasound. Thyroid fine needle aspiration was compatible with multinodular goiter (normal follicular cells, free colloid, macrophages with pigment). IV treatment with amoxicillin-clavulanic acid 1 g t.i.d. was administered for 2 weeks, with a decrease in temperature and normalization of the leukocyte level. Oral antibiotic treatment with amoxicillin-clavulanic acid was continued for 10 more days, followed by 25 days of ciprofloxacin for the osteomyelitis. Local treatment included saline soakings followed by application of Promogran (Johnson & Johnson, New Brunswick, NJ) and Kaltostat (ConvaTec Ltd., a Bristol-Myers Squibb Company, New York, NY) with slight improvement. At the same time, the patient was treated with warfarin sodium due to deep vein thrombosis under international normalized ratio 2-3. The patient was treated with IM testosterone once monthly for 1 year, which resulted in a reduction in the diameter and depth of the leg ulcers (Figure 3). Blood tests were not performed for follow-up of the immune state.

[The value of individual laboratory tests in the evaluation of inflammatory activity in rheumatoid arthritis].

In 65 patients with definite or classical rheumatoid arthritis (RA), according to ARA criteria, and the active disease, we studied the correlation of the clinical status (the number of the swollen and tender joints) with the following laboratory parameters: sedimentation rate, C-reactive protein, serum iron level, haemoglobin content and the number of erythrocytes, leucocytes and thrombocytes in the peripheral blood. All patients received nonsteroidal antiinflammatory drugs; 25,5% of them were on small daily doses of corticosteroids, and most of them (76,5%) were receiving some of the second-line drugs. The acceleration of the sedimentation rate was the most useful laboratory parameter and was found in 96,9% of the patients, followed by an increased quantity of the alpha-2 globulin, sideropenia and a decreased level of haemoglobin. Increase in the CRP titer was found in this study to be of a rather modest value and was increased in only 40% of the RA patients.

Anemia

A blood test will provide counts of white blood cells, red blood cells and platelets. If anemia appears, further tests may determine what type it is, and whether it has a serious cause. although of that, it is possible to refer to the genetic history and physical diagnosis. These tests may include: complete blood count (CBC); a CBC is used to count the number of blood cells in a sample of the blood. For anemia, it will likely to be interested in the levels of the red blood cells contained in blood (hematocrit), hemoglobin, mean corpuscular volume. determine the size and shape of red blood cells; some of red blood cells might also be examined for unusual size, shape and color. serum ferritin; This protein helps store iron in the body, a low levels of ferritin usually indicates a low levels of stored iron. serum vitamin B12; low levels usually develop an anemia, vitamin B12 is needed to make red blood cells, which carry oxygen to all parts of human body.

[Erythrocytosis in a 4 year-old child: diagnostic, prognostic, therapeutical problems].

Pure erythrocytosis is rare in children. This report describes such a case. A 4 year-old boy was admitted because erythrocytosis had been found routinely before adenoidectomy. He was born in Guatemala, was adopted just after his birth, and had been living in France since that age. Clinical examination was normal. His hemogram showed: erythrocytes: 8,800,000/mm3; hemoglobin: 20.1 g/dl; hematocrit: 66.8%; reticulocytes: 262,000/mm3; platelets: 200,000/mm3; leukocytes: 6,800/mm3. The patient had been given iron salts for the past 3 months without an earlier hemogram. Total red cell mass was 1200 ml (N: 600). The myelogram was normal as was the leukocyte alkaline phosphatases, serum lysozyme and vitamin B12. Blood ferritin was low (3.5 ng/ml). In vitro cultures of erythroid precursors were normal, as was the karyotype of myeloid cells. Blood erythropoietin concentration was 20-293 mU/ml (N:4-14). All the causes of secondary polycythemia were eliminated by appropriate investigations. The patient was treated by phlebotomy in aliquots of 25 ml/kg, twice a month, for 10 months, and was given iron therapy. At the end of treatment, his hemoglobin was 14 g/dl and his hematocrit was 45%. Both progressively increased again one year later, requiring new phlebotomies. The patient was followed for 4 years but no cause for this erythrocytosis was found; it was probably congenital in origin. This case of pure erythrocytosis was associated with elevated erythropoietin production. Whether this high secretion is related to receptor dysfunction remains to be determined.

Adult-onset Still's Disease as a Differential Diagnosis in Prolonged Fever: Diagnosis and Treatment Experience.

Adult onset Still's disease is a rare systemic disease that may involve many organs and may mimick many disease such as infection, autoimmune disease, and also malignancy. The diagnostic approach and treatment strategies have not been well established due to its rarity; however, there are some diagnostic criteria that may help. We present a case of 36-year old man who experienced high prolonged fever which firstly thought as infection. He also had unilateral wrist and knee joint pain and maculopapular rash. Laboratory examination showed high leukocytes count with elevated polymorphonuclear neutrophil count, high platelet count, high ferritin level, and negative results of many infection markers (typhoid antibody, procalcitonin, malaria test, blood culture, urine culture, IgM pneumonia, ASTO, syphilis test, antiHIV, HBsAg, antiHCV, etc). Chest X-ray, joint X-ray, ultrasonography, and echocardiography showed normal result. The patient was then diagnosed with Adult-onset Still's disease and received intravenous methylprednisolone and the fever was disappeared in 3 days. Six months later the arthralgia appeared again, methotrexate was administered and the pain was then relieved.

Prevalence of hematinics deficiency amongst female students and its correction.

Nutritional anemia (NA) is common in India. While iron deficiency (ID) is a well recognized cause of NA, prevalence of deficiencies of other hematinics is not systematically investigated. Seventy students of a junior class of a polytechnic and 202 inmates of girl students home were taken up for study. Students were given a questionnaire to elicit anemia related symptoms. Blood was collected for complete blood count (CBC), serum ferritin, folic acid and vitamin B12. Students of polytechnic received hematinic at bed time during their menstrual periods whereas inmates of students home received hematinic at bed time, 3 days in a week. After 6 months blood tests were repeated in those who completed the treatment. CBC was done on Coulter counter and ferritin, folic acid and vitamin B12 were assayed by chemiluminescence. Students were divided into three groups-(1) Control group with Hb 12.0 g/dl or more and ferritin 15.0 ng/ml or more; (2) ID Group with Hb 12.0 g/dl or more and ferritin less than 15.0 ng/ml; and (3) Iron Deficiency Anemia (IDA) group with Hb less tha 12.0 g/dl and ferritin less than 15.0 ng/ml. Basal parameters of three groups were compared using students t test. Change in parameters with treatment was compared using paired students t test. Median age-16 years (range 10-25). Anemia ( Hb < 12.0 g/dl)-94 (34.6%); MCV < 80 fl-153 (56.3%); MCH < 27 pg-167 (61.4%); Ferritin < 15.0 ng/ml-161 (59.2%); Folic acid < 3.5 ng/ml-34 (12.5%); Vitamin B12 < 258 pg/ml-133 (48.9%) Pre-therapy: (1) Hb, MCV, MCH and ferritin significantly lower in ID and IDA Groups compared to control group. (2) Hb, MCV, MCH and Ferritin significantly lower in IDA Group as compared to ID Group.  POST-THERAPY: (1) IDA group showed significant increase in Hb, MCV, MCH, ferritin, folic acid and vitamin B12. (2) final Hb (11.26+1.07) and ferritin (7.46+4.81) in IDA Group were subnormal. (3) MCV, MCH, ferritin, folic acid and vitamin B12 increased significantly in ID Group and control group. (1) Nutritional anemia is common amongst asymptomatic young female students. (2) Deficiencies of iron, folic acid and vitamin B12 are common and coexist. (3) 105 mg elemental iron for 3 days in a week for 6 months is not adequate to correct IDA. (4) 105 mg iron for 3 days in a week is enough to correct ID. (5) Non-anemic individuals with ID have iron deficient erythropoiesis. (6) Non-anemic individuals without ID, in this cohort, also had iron deficient eryhtropoiesis.

Adult onset Still's disease: review of 41 cases.

To describe the clinical, laboratory and radiological features, treatment and prognosis of patients with adult onset Still's disease (AOSD). Specific clinical features were retrospectively recorded in 41 patients fulfilling the Yamaguchi criteria. Patients were reviewed in two academic hospitals with a referral area of 700,000-1,000,000 inhabitants. Laboratory tests including haemogram, ferritin, biochemistry and autoimmunity were reviewed. Radiological studies, treatment and ACR functional class were determined. Forty-one patients with AOSD were identified, 25 of whom were female. Mean age at diagnosis: 38.19 years (range 17-68). Feverish polyarthritis was the most common clinical presentation. Acute phase reactants were invariably high in all patients. Serum ferritin levels were elevated in 86% of patients. Anti-cyclic citrullinated peptide antibodies (anti-CCP antibodies) were negative in all patients except one. The course of the disease was monocyclic in 44% of the patients, polycyclic in 26%, and chronic articular in 30%. ACR class was as follows: 29 (72.5%) class I, 7 (17.5%) class II, 2 (5%) class III and 2 (5%) class IV. As for the treatment received, aspirin or NSAIDs controlled the disease in eight patients (19.5%) and high-dose corticosteroids (0.5-1 mg/kg/day) in 32 (78%). Almost half of the patients (49%) required an additional diseasemodifying agent, usually methotrexate. Finally, in seven of them (17%) a biological treatment with TNF-α or specially anti-IL-1 had to be added to control the disease. The clinical and laboratory findings were similar to previous studies. Anti-CCP antibodies were almost always negative. A monocyclic course was associated with a good prognosis. Most of the patients were in ACR functional class I and II. Biological agents were required in 7 patients (17%).

Rowell Syndrome in Nigeria: Systemic Lupus Erythematosus Presenting as Recurrent Erythema Multiforme in a Young Woman.

Dear Editor, Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by diverse patterns of auto-antibody production with multi-organ affectation. Cutaneous involvement, either alone or in association with other systemic illnesses, is one of its most common manifestations (1). Dermatologic disorders like malar and discoid rashes are quite suggestive of SLE. However, the occurrence of non-specific skin lesions like erythema multiforme (EM) in patients with SLE (Rowell syndrome) can rarely occur (1). In such patients, a diagnosis of SLE may be missed or delayed in the absence of other overt clinical features of lupus. Herein we report a case of recurring EM-like eruptions as the cardinal cutaneous manifestation of previously undiagnosed, active SLE in a young Nigerian woman. A 26-year-old Nigerian woman presented with a three-day history of non-pruritic, generalized, and target-like, erythematous annular patches and plaques which mostly affected the trunk. A few lesions had presented with crusting and erosions at the time of examination (Figure 1). Associated symptoms included oral painful ulcers, low grade fever, and malaise. The patient had no other systemic symptoms and her prior drug history was not remarkable. Her erythrocyte sedimentation rate (ESR) was 66 mm/hour using the Westergren method. Screening for HIV and hepatitis B and C was negative. Herpes simplex, cytomegalovirus, and Epstein Barr viruses could not be screened for. Other baseline investigations (complete blood count, electrolytes, urea and creatinine as well as urinalysis) were within normal limits. The patient was managed as a case of EM of an unidentified inciting agent and her symptoms resolved with supportive care and antibiotics. However, she developed a recurrence about 5 weeks later, with more extensive and coalescent skin lesions (Figure 2). Additionally, there was a new onset of alopecia and pain in the small joints of the hands as well as both knees and ankles. At this time, the patient's ESR had gone up to 112 mm/h and she had developed significant proteinuria, with a protein creatinine ratio of 1.3 g/g (reference <0.5 g/g). Her antinuclear antibody (ANA) titer was high (1:320) with a speckled pattern. Anti-Smith antibody was also positive. A renal biopsy was declined. A tentative diagnosis of Rowell syndrome was made. The patient was started on high-dose steroids and hydroxychloroquine 200 mg twice daily. Subsequent care included the use of mycophenolate mofetil 1 g twice daily for 6 months. This was then changed to azathioprine at 50 mg twice daily. Follow-up after 6 months showed sustained clearance of skin lesions, resolution of fever and joint pains, as well as improvement in the renal profile, with a urine protein-creatinine ratio of 0.77 g/g. The presence of systemic lupus erythematosus, EM-like lesions, and a speckled pattern of antinuclear antibody in our patient fulfils the revised diagnostic criteria for RS put forward by Zeitouni et al. at the turn of the twenty-first century (2). Considering the rarity of EM-like lesions in SLE and the possibility of constitutional symptoms in EM, a diagnosis of RS may be readily overlooked in patients like the one described, whose major cutaneous manifestation of severe active SLE was EM-like lesions. In contrast to classic EM, where skin lesions are concentrated in the extremities, a predominant truncal distribution of EM-like lesions as found in our patient may favor a clinical consideration of RS (3). However, some authors have challenged the existence of Rowell syndrome as a distinct clinical laboratory entity. Arguments put forward in this regard include the fact that none of the immunological markers that have been described in RS are specific to any disorder. Additionally, the annular polycyclic dermatosis seen in sub-acute cutaneous lupus erythematosus (SCLE) can be difficult to clinically and histologically differentiate from EM (4,5). Patients with SLE also have a higher likelihood of developing adverse drug reactions (6). The inherent complexity of SLE may make for delayed and oftentimes difficult diagnosis, especially in a country where immunologic tests are expensive and rheumatologists are scarce. When patients do occasionally present with recurrences of skin lesions in the spectrum of EM, Steven-Johnson syndrome, and toxic epidermal necrolysis in the absence of a definite inciting agent, undiagnosed lupus may indeed be present in some of these individuals and should be considered in the differential diagnosis. In conclusion, while it is very rare, SLE may present first with recurrent episodes of EM-like rash. Despite the various possibilities which underlie their association, prompt identification and treatment of SLE in patients presenting with EM is important to prevent death or irreversible organ damage.

Severe vitamin B12 deficiency in an exclusively breastfed 5-month-old Italian infant born to a mother receiving multivitamin supplementation during pregnancy.

In infants, vitamin B12 deficiency may be due to an inborn error of absorption and metabolism, or nutritional problems. An exclusively breastfed 5-month-old Italian male infant, who was born after a normal full-term pregnancy to a vegan mother who was apparently daily treated with a multivitamin oral preparation during the second and third trimester, was hospitalised because of poor weight gain, feeding difficulties, severe pallor, muscle hypotonia and somnolence. Upon admission, his weight, length and head circumference were below the third percentile, he had an enlarged liver and spleen, and showed a significant delay in developmental milestones and communicative reactions. He had a hemoglobin level of 4.7 g/dL with an MCV of 84.2 fL, a white blood cell count of 4,680/mm3, and a platelet count of 45,000/mm3. His serum vitamin B12 level was 57 pg/mL (normal value 180-500 pg/mL) and serum folate level 12.8 ng/mL (normal value >3 ng/mL). The results of metabolic examinations excluded a cobalamin C disorder, whereas nutritional screening showed a serum iron concentration of 9 μg/dL and serum ferritin of 4 ng/mL. Magnetic resonance imaging of the brain showed mild dilatation of the lateral ventricles with diffuse delayed myelination. The child was diagnosed as having vitamin B12 and iron deficiency due to nutritional inadequacy and was immediately treated with packed red blood cells, intramuscular vitamin B12 injections, and iron supplementation. A few days after the start of therapy, his hemoglobin levels and other hematological parameters rapidly improved, and a clinical improvement was observed within few weeks. There was an increase in his achievement of developmental milestones, but his development was still retarded seven months after the start of therapy. This case underlines the importance of adequately controlling maternal vitamin B12 intake during pregnancy by means of supplementation which, in the case of vegan mothers, should be significantly greater than that usually given. Moreover, the supplementation should be continued during lactation in order to avoid the development of signs of deficiency that may be associated with persistent neurological problems in infants. The case also highlights the need to consider vitamin B12 deficiency in infants with severe anemia even if their hematological parameters do not indicate megaloblastic anemia because the concomitant presence of substantial iron deficiency may modify the characteristics of the anemia.

Elderly female with Autoimmune hemolytic anemia.

Autoimmune hemolytic anemia (AIHA) is a rare disease with an estimated prevalence of around 17/100,000. It is often difficult to diagnose and treat AIHA, especially in elderly. A 60-year-old female was admitted with the complaints of low grade fever, on-off for 6 months, progressive fatigue and dyspnea on exertion. She was transfused with three units of blood within these 6 months. Examination revealed pallor, edema, hemic murmur, and palpable liver. Hb was 2.9 gm%, T Bil 5.2 mg/dl, ESR 160 mm, and reticulocyte count 44.05%. Direct Coombs test was positive, anti-nuclear antibody (ANA) and Anti ds DNA were positive. A diagnosis of systemic lupus erythematosus (SLE) with AIHA was considered and patient was transfused with two units of packed red cells and put on steroid (prednisolone) at 1 mg/kg body weight daily. After 3 weeks, her Hb had increased to 10.4 gm% with gross clinical improvement.

InternalMed_Harrison

clinical features AIHA is a serious condition; without appropriate treatment, it may have a mortality of approximately 10%. The onset is often abrupt and can be dramatic. The hemoglobin level can drop, within days, to as low as 4 g/dL; the massive red cell removal will produce jaundice; and sometimes the spleen is enlarged. When this triad is present, the suspicion of AIHA must be high. When hemolysis is (in part) intravascular, the telltale sign will be hemoglobinuria, which the patient may report or about which we must enquire or test for. The diagnostic test for AIHA is the direct antiglobulin test developed in 1945 by R. R. A. Coombs and known since by this name. The beauty of this test is that it detects directly the pathogenetic mediator of the disease, i.e., the presence of antibody on the red cells themselves. When the test is positive, it clinches the diagnosis; when it is negative, the diagnosis is unlikely. However, the sensitivity of the Coombs test varies depending on the

A case of pancytopenia secondary to low-dose pulse methotrexate therapy in a patient with rheumatoid arthritis and renal insufficiency.

Most reports on serious MTX toxicity have focused on hepatic abnormalities, while other effects, including hematologic reactions, have not been emphasized. We experienced a case of pancytopenia secondary to MTX therapy in a patient with RA and renal insufficiency. A 67-year-old woman with a 12-year history of active seropositive RA that was a response to non-steroidal anti-inflammatory drugs, hydroxychloroquinine and intra-articular steroid injections, had been followed up and was diagnosed as early chronic renal failure in October, 1993. Recently, because of significant morning stiffness and polyarthralgia, the decision was made to institute MTX treatment. This was begun as a single oral dose of 5mg/week. After 2 doses, the patient was admitted to the hospital with general weakness. Laboratory tests showed a hemoglobin level of 7.9 g/dl, WBC count 1800/mm3 and platelet count of 64000/mm3. The serum creatinine level was 6.1 mEq/dl and the BUN level was 82 mEq/dl. Liver function test results were normal, but the serum albumin level was 2.7 g/dl. The patient subsequently developed fever and blood transfusions, granulocyte colony stimulating factor (G-CSF) and intravenous prophylactic antibiotic therapy were required. Her condition was improved. In summary, Low-dose MTX-related adverse hematologic side effects, including fatal pancytopenia, are rare but are a cause of increasing concern in patients with RA and renal insufficiency. Close monitoring of associated risk factors, particularly impaired renal function, should be mandatory for all patients who are receiving MTX therapy.