The skin and pediatric hematology. Dr. Machiel van den Akker Kinder hematologie oncologie ZNA Koningin Paola Kinderziekenhuis Herfst symposium 2018
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1 The skin and pediatric hematology Dr. Machiel van den Akker Kinder hematologie oncologie ZNA Koningin Paola Kinderziekenhuis Herfst symposium 2018
2 The skin and pediatric hematology Since it is impossible to discuss the whole pediatric hematology, I will only give some examples in which the skin is involved in the presentation of a hematologic problem.
3 Pale skin
4 Pale skin
5 Iron deficiency anemia Hb 7 g/dl MCV 56 fl MCHC 30 g/dl RDW 22 % Red blood cells 3.4x10E12/L Reticulocytes 1.5 % WBC 8.5x10E9/L ANC 2500x10E6/L Platelets 545x10E9
6 Pale skin BUT previously fit two-year-old girl two weeks ago viral URTI Hb 5.5 g/dl MCV 79 fl MCHC 34 g/dl RDW 17 % Red blood cells 2.3x10E12/L Reticulocytes 0.1 % WBC 8.5x10E9/L ANC 1500x10E6/L Platelets 383x10E9/L
7 Transient Erythroblastopenia of Childhood
8 Pale skin Not sick, looks pale. Pronounced large forehead, broadened face. Abdomen: liver 2 cm, spleen 2-3 cm.
9 Pale skin Hb 5.7 g/dl MCV 67 fl MCHC 32 g/dl RDW 22 % Red blood cells 2.51x10E12/L Reticulocytes 3.5 % WBC 12x10E9/L ANC 4700x10E6/L Platelets 244x10E9/L
10 Beta Thalassemia Major
11 Pale skin Always small child
12 Fanconi anemia -Rare genetic disease resulting in impaired response to DNA damage. -Majority develop cancer, most often acute myelogenous leukemia, and 90% develop bone marrow failure by age 40.
13 Pale skin This morning everything normal, but now after lunch outside (pita).
14 Pale skin Hb 4.1 g/dl MCV 92 fl MCHC 32 g/dl RDW 18 % Red blood cells 1.6x10E12/L Reticulocytes 11 % WBC 13.4x10E9/L ANC 4920x10E6/L Platelets 211x10E9/L
15 G6PD deficiency -Jaundice and fatigue after eating fava beans; family history revealed a paternal aunt who was not allowed to eat fava beans. -Spectrophotometric analysis revealed: G6PD 0.1 U/g Hb.
16 Pale skin Apparently often with fever, this 17 year old girl has icteric sclera (like her Danish father). Her spleen 3cm palpable.
17 Pale skin Hb 11.1 g/dl MCV 80 fl MCHC 37.5 g/dl RDW 16.5 % Red blood cells 4.1x10E12/L Reticulocytes 13 % WBC 6.5x10E9/L ANC 2100x10E6/L Platelets 167x10E9/L
18 Hereditary spherocytosis
19 Petechial rash
20 Petechial rash Not sick, physical examination otherwise normal. Hb 12 g/dl MCV 76 fl MCHC 32.5 g/dl RDW 16 % Red blood cells 4.5x10E12/L Reticulocytes 4 % WBC 6.5x10E9/L ANC 2100x10E6/L Platelets 2x10E9/L
21 Acute Idiopathic Thrombocytopenic Purpura Necessary investigation only CBC and blood film, on the condition that physical examination is normal, besides petechiae and purpura. Therapy: -observation -IVIg -steroids -antid (-IV Rituximab (anticd20) -PO Revolade)
22 Petechial rash
23 Petechial rash 14 year-old-boy, tired, bone pain, and fever. Hb 7.5 g/dl MCV 80 fl MCHC 32.1 g/dl RDW 16.5 % Red blood cells 3.2x10E12/L Reticulocytes 2 % WBC 27x10E9/L ANC 1466x10E6/L Blasts 13500x10E6/L Platelets 14x10E9/L
24 Acute Lymphoblastic Leukemia Childhood acute lymphoblastic leukemia (ALL) is a type of cancer in which the bone marrow makes too many immature lymphocytes.
25 Petechial rash
26 Petechial rash Boy is brought to his pediatrician for easy bruising, multiple hospital stays due to pneumonia and otitis media infections as well as recurrent epistaxis. Petechiae and purpura in multiple areas, eczematous patches are also found on his flexural surfaces, mild hepatosplenomegaly. Hb MCV MCHC 8.9 g/dl 59 fl 32 g/dl RDW 18.5 % Red blood cells Reticulocytes 3 % WBC ANC Platelets 2.8x10E12/L 8.9x10E9/L 2500x10E6/L 30x10E9/L
27 Wiskott-Aldrich Syndrome -Mostly X-linked recessive, primary immunodeficiency disorder of B and T cells. -Pathogenesis mutation in WAS gene encoding Wiskott-Aldrich syndrome protein (WASp) impaired actin cytoskeleton results in defective T cell signalling and interactions with APCs also impairs phagocytosis and chemotaxis loss of cellular and humoral response -To remember (WATER) o Wiskott o Aldrich o Thrombocytopenic purpura o Eczema o Recurrent infections
28 Petechial rash, not always hematology
29 Petechial rash, not always hematology Enterovirus infection, but many other viruses and bacteria can be responsible.
30 Petechial rash, not always hematology
31 Petechial rash, not always hematology Caused by emesis, due to rupture of capillaries in the upper dermis resulting from elevated intravascular pressure during vomiting.
32 Purpura
33 Purpura Infant (boy), fell, some old and new bruises. Grandfather had the same, died young. Hb 9.0 g/dl MCV 72 fl MCHC 32 g/dl RDW 16.5 % Red blood cells 3.5x10E12/L Reticulocytes 4 % WBC 6.5x10E9/L ANC 2700x10E6/L Platelets 278x10E9/L
34 Hemophilia A INR aptt 0.99 s 75 s -Hemophilia A is an X-linked, recessive disorder caused by deficiency of functional plasma clotting factor VIII (FVIII), which may be inherited or arise from spontaneous mutation. -Normal values for FVIII assays are %. Values in hemophilia A are as follows: Mild: >5% Moderate: 1-5% Severe: < 1%
35 Purpura
36 Purpura 8 month-old girl, always purpura, ecchymosis and some petechiae, sometimes epistaxis. Hb 10.2 g/dl MCV 69 fl MCHC 32.5 g/dl RDW 19 % Red blood cells 3.9x10E12/L Reticulocytes 5 % WBC 11x10E9/L ANC 2570x10E6/L Platelets 312x10E9/L D-dimers INR aptt fibrinogen LDH CRP 0.2 nmol/l 1.0 s 29 s 200 mg/dl 711 u/l 2 mg/l
37 Glanzmann thrombasthenia Plaatjesfunction abnormal -Aggregation studies: no aggregation with epinefrin and ADP clear aggregation with ristocetin suggestive for Glanzmann thrombastenia -Flow cytometry confirms the absence of the GPIIa/GPIIIb receptor on the platelet (very low CD31 en CD61). -Rare, AR bleeding disorder, characterized by the failure of platelets to bind fibrinogen and aggregate after stimulation by physiologic agonists due to defective integrin GPIIb/IIIa. -Treatment: exacyl, platelet infusie, FVIIa (BMT).
38 Purpura
39 Purpura 11-year-old, sick, high fever, vomiting, headache. Hb 5.6 g/dl MCV 74 fl MCHC 31.7 g/dl RDW 24% Red blood cells 2.3x10E12/L Reticulocytes 3 % WBC 28.4x10E9/L ANC 25800x10E6/L Platelets 4x10E9/L
40 Disseminated Intravascular Coagulation D-dimers INR aptt fibrinogen LDH CRP 4.5 nmol/l 2.5 s 68 s 85 mg/dl 3288 u/l 255 mg/l Early antibiotic treatment. Full supported treatment.
41 Purpura
42 Blueberry Muffin Syndrome 2.5-month-old baby girl, 7-day course of multiple bluish skin nodules and a 2-day history of poor activity, decreased appetite, and respiratory distress. Hb 3.5 g/dl MCV 74 fl MCHC 31.8 g/dl RDW 18.9 % Red blood cells 1.2x10E12/L Reticulocytes 1.8 % WBC 79.9x10E9/L Blasts 15900x10E6/L Platelets 50x10E9/L
43 Acute Myeloid Leukemia Biopsy of the skin lesion: infiltrates of monotonous blast-like cells. Immunohistochemically, the diagnosis was acute myeloid leukemia.
44 Blueberry Muffin Syndrome Descriptive term used when an infant is born with multiple blue/purple marks or nodules in the skin. These are due to the presence of: -clusters of blood-producing cells in the skin (extramedullary erythropoiesis), -or bleeding into the skin (purpura) -or spreading cancer (metastases)
45 Blueberry Muffin Syndrome There are many underlying causes that need to be considered when a baby presents with blueberry muffin syndrome. These include: Tumors such as: Congenital leukemia cutis Langerhans cell histiocytosis Neuroblastoma Congenital rhabdomyosarcoma Blood disorders such as: Hemolytic disease of the newborn rhesus or ABO incompatibility Hereditary spherocytosis Twin-twin transfusion syndrome Congenital infections such as: Rubella, Toxoplasmosis, Cytomegalovirus, Herpes simplex, Coxsackie virus, Parvovirus, Epstein Barr virus, and Syphilis
46 Purpura, not always hematology
47 Purpura, not always hematology Henoch Schonlein Purpura
48 Purpura, not always hematology
49 Purpura, not always hematology Papular Purpuric Gloves and Socks Syndrome because of a Mycoplasma Infection.
50 Purpura, not always hematology
51 Purpura, not always hematology Acute hemorrhagic edema of infancy -A self-limiting, benign leukocytoclastic vasculitis that is more common in male infants. -Unclear, but it is believed to be due to an immune complex-mediated hypersensitivity reaction in the small blood vessels, has been associated with prodromal illnesses or medication use.
52 Purpura, not always hematology
53 Purpura, not always hematology Trauma/factitial purpura
54 Purpura, not always hematology
55 Purpura, not always hematology Abuse
56 Other skin lesions
57 Other skin lesions seborrheic dermatitis bilateral otorrhea splenomegaly Hb 10 g/dl MCV 64 fl MCHC 32 g/dl RDW 17.1 % Red blood cells 3.7x10E12/L Reticulocytes 1.6 % WBC 12.5x10E9/L ANC 5600x10E6/L Platelets 211x10E9/L
58 Langerhans Cell Histiocytosis diagnosis based on histopathological examination: characterized by multinucleated Langerhans' cells, histiocytes and eosinophils. EM examination: Birbeck granules (gold standard). Immunohistochemistry: diagnosis can be established with the use of CD1a, S100, CD45, and/or Langerin immunostaining on histopathological specimens. S100 positivity
59 Other skin lesions Long-standing lesion.
60 Primary Cutaneous B-Cell Lymphoblastic lymphoma Punch biopsy specimen of the left cheek at original magnification 409 showing medium-sized atypical lymphoid cells staining diffusely positive for TdT (dysplasia).
61 Other skin lesions
62 Sweet syndrome -Rare skin condition. -Fever and painful skin lesions that appear mostly on your arms, neck, head and trunk. -Sometimes triggered by an infection, illness or certain medications. -Treatment: steroids. -Recurrence is uncommon.
63 Other skin lesions
64 Other skin lesions -Rash of sudden onset consisting of erythematous macules on both cheeks that were neither itchy nor tender and did not blanch. -Over the next week, the rash spread from her cheeks to her arms, back, thighs and buttocks, and became papular and darker. -No other symptoms. -Referred to a pediatric dermatologist.
65 Other skin lesions
66 Acute Lymphoblastic Leukemia -Afterwards physical examination showed hepatosplenomegaly, blood test done. -Bone marrow aspirate confirmed T-cell ALL with 80% 85% blast cells. Hb 11.5 g/dl MCV 80 fl MCHC 32.1 g/dl RDW 16.5 % Red blood cells 4.5x10E12/L Reticulocytes 2 % WBC 17.7x10E9/L ANC 35x10E6/L Blasts 16.6x10E9/L Platelets 175x10E9/L
67 Other skin lesions
68 Livedo reticularis -5-month-old girl, presented with a rash, fever, no clear focus of fever. -Within hours getting pale and icteric sclera. Hb 6.1 g/dl MCV 81 fl MCHC 32 g/dl RDW 16.5 % Red blood cells 1.9.1x10E12/L Reticulocytes 12 % WBC 6.5x10E9/L ANC 2670x10E6/L Platelets 245x10E9/L Bilirubin, total LDH Haptoglobin 6.4 mg/dl 2140 U/L 0.1 mg/dl
69 Livedo reticularis The picture is a little girl with IgA auto Immune hemolytic anemia.
70 Livedo reticularis Antiphospholipid syndrome Livedoid vasculopathy Cryoglobulinaemia Multiple myeloma Cold agglutinin disease Protein C and S deficiency Antithrombin III deficiency Disseminated intravascular coagulation Haemolytic uraemic syndrome Deep venous thrombosis
71 The skin and pediatric hematology Just examples. Presentation of a hematologic problem can be quite diverse.
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