حسین سلطان زاده
استاد دانشگاه علوم پزشکی شهید بهشتی
متخصص کودکان ونوزادان
طی دوره بالینی عفونی از میوکلینیک آمریکا
دبیر برگزاری کنفرانس های ماهیانه گروه اطفال
دانشگاه علوم پزشکی شهید بهشتی
فوق تخصص عفونی اطفال
بخش عفونی و تحقیقاتی بیمارستان
دکترزهرا چاوشی زاده
فوق تخصص آلرژی و ایمونولوژی
عضو هیئت علمی بیمارستان
Pneumo Cystis Carinii Pneumonia P.C.P
Arthritis as an uncommon manifestation of Hyper Ig M syndrome
A 9-month old male infant
presented to the emergency department with a 20-days history of cough, sneeze,
couriza and fever. He presented swelling of left knee with normal range of
motion since 15 days ago. His fever increased and he admitted at other hospital
before admission at our hospital and treated as septic arthritis there.
He suddenly presented
respiratory failure after dranage of his knee and referred to our hospital and
admitted in ICU.
He presented cough and
respiratory distress at 2 month-old but responded to usual treatment. After that
he had frequently common cold manifestation that responded to usual treatments.
He was born at 38 weeks
gestation with a birth weight of 3200 gr after uncomplicated pregnancy, delivery
and nursery course. He resided with his mother, father, 2 siblings: His healthy
sister and his 10-year-old brother who presented arthritis at 3 years of his
life. He presented hematuria , proteinuria , priorbital edema and renal failure
and admitted in ICU since 3 month ago.
On examination, the
infant had a temperature of 38.5 'c, a pulse of 96 beats/min, a respiratory rate
of 54/min and a weight of 8.5 kg, with an oxygen saturation of 80.5% in room
air. He was lethargic and had subcostal and intercostals retraction in chest
examination, fine crackle in the base of both lungs.
A chest radiograph
showed diffused alveolar consolidation with airbronchogram. Hematologic studies
revealed a white cell count of 25,800/mm3 with a differential count of 57%
neutrophils, 43% lymphocyte ; hemoglobin 14.4 g/dl; and platelet count
Blood and urine cultures
were obtained, synovial fluid contained many white cell count with no bacteria.
Synovial fluid culture was negative.
The electrolytes, urine
analysis were all normal. Only LDH level showed rising to 1287 .
The patient was
hospitalized and empirically treated with
lavage showed Ecoli. An open lung biopsy was performed which revealed the
etiology of this infant's illness.
arthritis, hyper IgM syndrome,
Prompted by the unusual
radiographic findings, an immunology evaluation was performed. Quantitative
immunoglobulins were including IgG, IgA,IgM,IgE and complements (C3, C4). C3 and
C4 were normal.
Immunophentyping Analysis: CD3,CD4,CD8 ,CD1(1b),CD1(1c),CD16,CD56,CD11c were
decreased. CD1 (1a), CD19 were increased. CD18, CD11a, CD11b were normal. NBT
test was normal. HIV Ab/Ag was non reactive.
Ig M was increased, Ig G,
Ig A were decreased. IgE was normal.
immunoglobulin test shows high IgM level.
The open lung biopsy
revealed healing ARDS with pneumocystis carinii cysts.
A diagnosis of Hyper IgM
syndrome with pneumocytis carinii pneumonia was made. Therapy with ceftriaxone
was initiated. The patient was also given trimethoprim-sulfamethoxazole and IVIG.
Repeating chest radiography showed improvement after 17 days. He currently
receives monthly IVIG and prophylactic trimethoprim-sulfamethoxazole and he is
currently free of infection. First described by Rosen et al in 1961, XHIGM is
an inherited immunodeficiency resulting in a defect in immunoglobulins function.
Immunodeficiency with hyper-IgM
was described by Israel-Asselain
et al. in 1960
and Rosen et al.
1974, a World Health Organization (WHO) working party named the syndrome
immunoglobulin deficiency with increased IgM (hyper-IgM syndrome
It is characterized by recurrent
infections, very low or undetectable levels of IgG and IgA, normal to increased
Approach to Diagnosis
The primary immunodeficiencies characteristically present in
childhood with infections that persist for long duration with
multiple recurrences that are resistant to antibiotics. Failure to
thrive and developmental delay are significant clues to the
seriousness of their infections. Many immunodeficient children
develop other symptoms such as skin rashes, and many have associated
developmental anomalies of the face, skeletal system, heart, and
The nature of the pathogens and
sites of infections can provide insight as to the underlying
immunodeficiency. Defects involving B cell function result in
recurrent sinopulmonary infections, often with bacterial septicemia.
The lack of antibody production may also increase susceptibility to
invasive disease with enteroviruses, resulting in chronic viral
meningitis, and giardiasis. T cells are essential for the control of
viral and fungal disease, however they also provide helper function
to B cells for effective antibody responses. Thus, T cell disorders
present as combined T and B cell immunodeficiency with susceptibility
to both bacterial and chronic, invasive viral, and fungal pathogens.
Patients with disorders of granulocytes are susceptible to
staphylococcal diseases and gram-negative infections.
The primary immunodeficiencies are
commonly inherited disorders, thus a family history is one of the
best diagnostic clues. Unfortunately, because these diseases are rare
with low carrier frequencies, a negative family history does not rule
out a primary immunodeficiency. Furthermore, occurrence of new
mutations, especially for X-linked disorders, is so high that the
majority of patients with proven X-linked immunodeficiency mutations
have no history of affected male relatives.
Initial laboratory evaluation for immunodeficiency should include a
minimum of tests that can be performed reliably by any laboratory. The
initial screening should include a complete blood count and
quantitation of serum IgG, IgM, and IgA levels. Laboratories should
provide age-matched normal values for cell counts, immunoglobulin
measurements and proper controls for functional studies. Other
readily available tests are: 1) Quantification of blood mononuclear
cell populations: T cells (CD3, CD4, CD8, TCR ß,
TCR ); B cells (CD19, CD20, CD21, Ig); NK cells
(CD16/CD56); monocytes (CD15); activation markers (HLA-DR, CD25, CD80
for B cells), CD154 for T cells. 2) T cell functional evaluation:
delayed hypersensitivity skin tests (PPD, Candida, histoplasmin, and
tetanus toxoid); proliferative response to mitogens (anti-CD3
antibody, phytohemagglutinin, concanavalin A) and allogeneic cells
(mixed lymphocyte response); cytokine production. 3) B cell
functional evaluation: natural or commonly acquired antibodies;
response to immunization proteins and carbohydrate antigens; and
quantitative IgG subclass determination. 4). Phagocyte function:
reduction of nitroblue tetrazolium; chemotaxis assays, and bactericidal
The benefit of immunoglobulin (IG)
replacement in primary antibody deficiencies is unquestionable.
Treatment of XHIM is based on regular
administration of i.v. immunoglobulins and use of cotrimoxazole to prevent PCP
. Severe neutropenia responds to administration of recombinant granulocyte
colony-stimulating factor (G-CSF) . Prevention of liver disease is based on
careful monitoring of liver function, and on hygienic measures to avoid
infection (i.e. use of boiled or bottled water).
Despite all these measures, the mortality rate
remains very high in XHIM, and more aggressive forms of treatment have been
proposed. Liver transplantation has been attempted in a few cases with
sclerosing cholangitis, but relapse is common . In contrast, bone marrow
transplantation (particularly if performed early in life) from HLA-identical
family (and possibly also from matched unrelated) donors may cure the disease
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