Poikiloderma with Neutropenia

Excerpt

Clinical characteristics: Poikiloderma with neutropenia (PN) is characterized by an inflammatory eczematous rash (ages 6-12 months) followed by post-inflammatory poikiloderma (age >2 years) and chronic noncyclic neutropenia typically associated with recurrent sinopulmonary infections in the first two years of life and (often) bronchiectasis. There is increased risk for myelodysplastic syndrome and, rarely, acute myelogenous leukemia. Other ectodermal findings include nail dystrophy and palmar/plantar hyperkeratosis. Most affected individuals also have reactive airway disease and some have short stature, hypogonadotropic hypogonadism, midfacial retrusion, calcinosis cutis, and non-healing skin ulcers.

Diagnosis/testing: Often the diagnosis of PN can be established in a proband based on clinical findings (post-inflammatory poikiloderma and congenital chronic neutropenia). Unequivocal confirmation of the diagnosis of PN relies on detection of biallelic USB1 pathogenic variants on molecular genetic testing.

Management: Treatment of manifestations: Dermatologic manifestations are treated with gentle skin care using bland emollients and diligent sun protection; very pruritic palmar/plantar hyperkeratosis can be treated with a strong topical steroid or a topical keratolytic if secondary dermatophyte infection has been ruled out. Although use of granulocyte-colony stimulating factor (G-CSF) increases the absolute neutrophil count, there is little evidence of its clinical effect (such as decreased frequency of infections). Myelodysplastic syndrome and acute myelogenous leukemia are treated in the usual manner. Sinopulmonary, middle ear, and skin infections require aggressive treatment with antibiotics. Reactive airway disease and hypogonadotropic hypogonadism are treated in the usual manner.

Prevention of secondary complications: Annual influenza vaccine; dental cleaning and evaluation for gingivitis/caries every three to six months; liberal use of sunscreens with both UVA and UVB protection to reduce the risk of skin cancer.

Surveillance: Annual evaluation:

1. By a physician familiar with PN of CBC with differential and platelet count (for evidence of anemia and/or thrombocytopenia ‒ signs of possible myelodysplastic syndrome);

2. By a pulmonologist for those with bronchiectasis, chronic cough, and/or reactive airway disease;

3. By a dermatologist (starting at age 10 years) for skin cancer screening.

In children: routine monitoring of growth, developmental milestones, school progress, and pubertal development.

Agents/circumstances to avoid: Excessive sun exposure (to decrease risk of skin cancer); exposure to second-hand cigarette or wood smoke and persons with respiratory illnesses (to decrease the risk of respiratory infections).

Evaluation of relatives at risk: It is appropriate to evaluate apparently asymptomatic older and younger sibs of a proband in order to identify as early as possible those who would benefit from prompt initiation of treatment and surveillance for potential complications.

Genetic counseling: PN is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the USB1 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal and preimplantation genetic testing are possible.