History and exam

Key diagnostic factors

common

history of prior infections

Pathogens such as Aspergillus species, Nocardia species, Serratia marcescens, and Burkholderia cepacia, or recurrent infections with Staphylococcus aureus, may suggest CGD.[1][3][16][52]

shortness of breath

May indicate respiratory infection (e.g., pneumonia).

perianal pain

Along with constipation, pain on sitting and prior to a bowel movement, and a palpable mass, the patient may have a perianal abscess.

flank pain

May indicate genitourinary obstruction secondary to granulomatous masses.

red skin lesion

Skin bumps may indicate furuncles, which are often warm, painful, and pus-filled. May also be a sign of impetigo or infected eczema. Patients may have pityrosporum folliculitis.

abnormal chest examination

A decrease in breath sounds and crackles may indicate respiratory infection (e.g., pneumonia) or chronic lung disease.

rigors

May indicate infection.

fever

May indicate infection.

chronic lymphadenopathy

Patients often have chronic lymphadenopathy.[39]

poor growth

Patients often have poor growth.[40]

joint pain

Found in female carriers of gp91phox mutations.[36] May also accompany osteomyelitis. Joint may be warm.

facial pain

May accompany sinusitis, along with poor nasal air flow, headache, and yellow discharge.

chorioretinal lesions

Occur in 25% to 35% of patients.[53][54]

skin scarring

May be due to multiple skin infections.

Other diagnostic factors

common

fatigue

May accompany various infections.

diarrhea

Often recurrent; may be a sign of enterocolitis.

May be bloody.

abdominal pain

May indicate enterocolitis.

cough

May indicate respiratory infection (e.g., pneumonia) or chronic lung disease.[35]

anorexia

May indicate infection.

arthralgias

May indicate infection. Also seen in female carriers of gp91phox mutations.

nausea and vomiting

May indicate various infections, but also gastrointestinal or genitourinary obstruction secondary to granuloma formation.

bloody urine

May indicate genitourinary infection or obstruction.

abnormal urinary flow

Patients with genitourinary obstruction secondary to granuloma formation may be unable to pass urine or may have an interrupted or weak flow.

hepatosplenomegaly

Patients often have hepatosplenomegaly.[40]

uncommon

family history of discoid lupus

Found in female carriers of gp91phox mutations.[36]

oral ulcer

Found in female carriers of gp91phox mutations.[36]

skin rash

Found in female carriers of gp91phox mutations.[36]

Risk factors

strong

family history of CGD

There may be a history of CGD within the family or family members with recurrent infections.

A third of X-linked cases arise de novo.[3]

age <5 years

Most patients are diagnosed before the age of 5.[3]

male sex

The majority of patients are male, as the X-linked form is most common.

abnormally skewed X chromosome inactivation in X-linked carriers

Female carriers of X-linked disease can develop infectious complications if <10% of neutrophils are normal.[1][3][27][28][29]

weak

myeloperoxidase and FCgammaRIIIb polymorphisms

Polymorphisms of the genes encoding myeloperoxidase and FCgammaRIIIb are associated with increased risk of gastrointestinal complications.[30]

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