caso clinico 1

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Casos clínicos
Luisa Ortega was born at full term and weighed 3.7 kg. She was the second child born to the Ortegas. At 4 weeks of age, Luisa 
was taken by her parents to her pediatrician because she had swelling and redness around the umbilical cord stump 
(omphalitis), and a fever of 39ºC. Her white blood cell count was 71,000 μl –1 (normal 5000–10,000 μl –1). She was treated in 
the hospital with intravenous antibiotics for 12 days and then discharged home with oral antibiotics. At the time of discharge 
her white blood count was 20,000 μl –1. Cultures obtained from the inflamed skin about the umbilical stump before antibiotic 
treatment grew Escherichia coli and Staphylococcus aureus.
The Ortegas had had a baby boy 3 years before Luisa’s birth. At 2 weeks of age he developed a very severe infection of the 
large intestine (necrotizing enterocolitis). Separation of his umbilical cord was delayed. He subsequently suffered from 
multiple skin infections and he died of staphylococcal pneumonia at 1 year of age. Just before his death his white blood cell
count was recorded at 75,000 μl –1. Because of the previous family history, Luisa was referred to the Children’s Hospital. At the 
time of her admission to the Children’s Hospital she seemed normal on physical examination, and radiographs of the chest and 
abdomen were normal.
Because of the previous family history, Luisa was referred to the Children’s Hospital. At the time of her admission to the 
Children’s Hospital she seemed normal on physical examination, and radiographs of the chest and abdomen were normal. 
Cultures of urine, blood, and cerebrospinal fluid were negative. Her white blood count was 68,000 μl –1 (very high). Of her 
white cells, 73% were neutrophils, 22% lymphocytes, and 5% eosinophils (this distribution of cell types is in the normal range 
but the absolute count for each is abnormally high). Her serum IgG concentration was 613 mg dl–1 (normal), her IgM was 89 
mg dl–1 (normal), and her IgA 7 mg dl–1 (normal). The concentration of complement component C3 in her serum was 185 mg 
dl–1 and that of C4 was 28 mg dl–1 (both normal).
Caso clínico 1
At 4 weeks of age, Luisa was taken by her parents to her pediatrician because she had swelling and redness around the 
umbilical cord stump (omphalitis), and a fever of 39ºC. Her white blood cell count was 71,000 μl –1 (normal 5000–10,000 μl –
1). (…) Of her white cells, 73% were neutrophils, 22% lymphocytes, and 5% eosinophils (this distribution of cell types is in the 
normal range but the absolute count for each is abnormally high).
Caso clínico 1
Inflamação local
Inflamação sistêmica
She was treated in the hospital with intravenous antibiotics for 12 days and then discharged home with oral antibiotics. At the 
time of discharge her white blood count was 20,000 μl –1. Cultures obtained from the inflamed skin about the umbilical stump 
before antibiotic treatment grew Escherichia coli and Staphylococcus aureus.
(…) swelling and redness around the umbilical cord stump (…)
Caso clínico 1
Infecção bacteriana na pele
Tratamento com antibióticos reduz a leucocitose
Lesão não é purulenta, ou seja, não há pus
Ausência de pus indica que não há neutrófilos 
Her serum IgG concentration was 613 mg dl–1 (normal), her IgM was 89 mg dl–1 (normal), and her IgA 7 mg dl–1 (normal). 
The concentration of complement component C3 in her serum was 185 mg dl–1 and that of C4 was 28 mg dl–1 (both normal).
Caso clínico 1
Concentrações de imunoglobulinas e proteínas do complemento estão normais
Resposta humoral está funcionando normalmente
Se a resposta inflamatória está funcionando normalmente, por que a paciente
está suscetível à infecção bacteriana?
Caso clínico 1
A leucocitose exagerada indica que os leucócitos 
estão sendo produzidos, mas que a migração das 
células para os tecidos pode estar comprometida.
De fato, a ausência de pus indica que neutrófilos 
não estão migrando para o sítio da infecção.
LAD, Leucosyte Adhesion Deficiency
O paciente apresenta uma deficiência genética 
que afeta moléculas de adesão expressas por 
leucócitos impedindo a migração para os tecidos
Principais observações Deficiência
Alterações genéticas que afetam o funcionamento das integrinas dos leucócitos
Caso clínico 1
Luisa Ortega was born at full term and weighed 3.7 kg. She was the second child born to the Ortegas. The Ortegas had a baby 
boy 3 years before Luisa’s birth. At 2 weeks of age he developed a very severe infection of the large intestine (necrotizing 
enterocolitis). He subsequently suffered from multiple skin infections and he died of staphylococcal pneumonia at 1 year of 
age. Just before his death his white blood cell count was recorded at 75,000 μl –1.
Caso clínico 1
O irmão da paciente faleceu devido a uma 
pneumonia bacteriana
Apresentou um quadro clínico semelhante, incluindo 
infecção na pele e leucocitose exagerada
Único tratamento para curar a doença é o
transplante de medula óssea
Funciona porque o problema é específico de
células hematopoiéticas, ou seja, a substituição
de células tronco hematopoiéticas do paciente
por células saudáveis de um doador corrige a 
deficiência
Se o problema fosse na expressão de moléculas 
de adesão de células endoteliais, o transplante 
não ajudaria
Doença do irmão indica problema genético Tratamento
Caso clínico 1
Diagnóstico de LAD
CD18
CD15
1
3
2
anti-CD18
anti-CD15
1 – pessoas normais
2 – deficiência de CD15 (problema no rolamento)
3 – deficiência de CD18 (problema de adesão)
gr
an
u
lo
si
d
ad
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tamanho
Randy Johnson, a 15-year-old high-school student, had a summer job working with a gardening crew. His job entailed 
spreading bark mulch in garden beds. At the end of August of that summer he rapidly developed severe shortness of breath, a 
persistent cough, and chest pain. Because of impending respiratory failure he was admitted to the hospital. A radiological 
examination of Randy’s chest was performed, which revealed the presence of large ‘cotton ball’ densities in both lungs. One of 
these lesions was aspirated with a fine needle; when the aspirate was stained, numerous fungal hyphae were seen. A culture 
of the aspirate grew Aspergillus fumigatus.
Randy was started on intravenous amphotericin B and assisted mechanical ventilation through a tracheotomy. He slowly 
improved over the course of two months. During this time in the hospital, he contracted two further respiratory infections, 
with Pseudomonas aeruginosa and Streptococcus faecalis. These infections were also treated with appropriate antibiotics.
At the time of his initial admission to the hospital, Randy’s white blood cell count was 11,500 μl –1 (normal 5000–10,000 μl –
1). He had 65% neutrophils, 30% lymphocytes, and 5% monocytes: these proportions are normal (Leucocitose e distribuição
normal de leucócitos).
Because of his infections, which were unusual for a seemingly healthy 15-year-old adolescent, Randy’s serum 
immunoglobulins were measured. The serum IgG level was 1650 mg dl–1 (the upper limit of normal is 1500 mg dl–1). IgM and 
IgA were in the high normal range at 250 and 175 mg dl–1, respectively (Produção normal de anticorpos).
His mother reported that Ralph had a perirectal abscess in infancy but had otherwise been well (Migração normal de 
neutrófilos).
His other three sisters and other brother had no major infectious problems (Doença genética associada ao cromossomo X –
gp91phox).
Caso clínico 2
Caso clínico 2
Alterações genéticas que impedem a produção de radicais
livres de oxigênio pela NADPH oxidase
Caso clínico 2
Presença de granulomas em vários órgãos
Caso clínico 2
Diagnóstico de doença granulomatosa crônica
Caso clínico 2
Único tratamento para curar a doença é o
transplante de medula óssea
Funciona porque o problema é específico de
células hematopoiéticas, ou seja, a substituição
de células tronco hematopoiéticas do paciente
por células saudáveis de um doador corrige a 
deficiência
Tratamento