Paroxysmal cold hemoglobinuria (PCH) is an autoimmune hemolytic anemia featured by complement-mediated intravascular hemolysis after cold exposure. It can present as an acute non-recurrent postinfectious event in children, or chronic relapsing episodes in adults with hematological malignancies or tertiary syphilis. Described by Julius Donath (1870–1950) and Karl Landsteiner (1868–1943) in 1904, PCH is one of the first clinical entities recognized as an autoimmune disorder. Signs and symptoms
Pediatric patients usually present with acute onset of hemolytic anemia with fatigue, exercise intolerance, pallor, jaundice, and hemoglobinuria, preceded by exposure to cold temperature and preceding viral-like illness. This may be complicated by acute renal failure due to nephrotoxic free hemoglobin and tubular obstruction. Although the disease may be fulminant during onset, the acute form generally follows a transient, self-limiting course.Chronic relapsing PCH manifests as episodic hemoglobinuria and anemic symptoms, usually milder than the acute form. While the classical syphilitic PCH becomes infrequent, paraneoplastic cause with underlying hematological malignancies especially in the elderly should be considered. Hepatosplenomegaly and adenomegaly are not pertinent to PCH, unless associated with underlying lymphoproliferative disorders. This form remains refractory if the underlying condition is not treated. Cause
Infectious agents are implicated in the acute form of PCH. Viral agents include measles, mumps, Epstein-Barr virus, cytomegalovirus, varicella-zoster virus, influenza virus, and adenovirus. Non-viral agents include Mycoplasma pneumoniae and Haemophilus influenzae. Chronic relapsing PCH is classically associated with syphilis, as well as hematological malignancies including non-Hodgkin lymphoma and myeloproliferative neoplasms. Pathophysiology
The exact pathogenesis is not fully elucidated.
During the first 6–12 months of age, there is increased sebum production stimulated by luteinizing hormone (LH) and testosterone of testicular origin that stops after this period until adrenarche. Girls do not experience this.Genetics and family history play a role in influencing sebaceous gland size and activity, pore size and inflammation that can increase risk of onset and presentation of infantile acne.It is suggested that the fetal adrenal gland along with testicular androgen could be the cause of infantile acne. During the neonatal period, there is increased sebum production through an enlarged zona reticularis (an androgen producing area) on the fetal adrenal gland that gradually decreases to very low levels at around 1 years of age, coinciding with when infantile acne tends to resolve. The fetal adrenal gland produces androgens such as dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) that stimulate sebaceous glands. Diagnosis
Diagnosis is based on presentation of comedones primarily on the face of an infant of 6–12 months of age. Severity can be mild, moderate or severe and can be determined from the presence and distribution of comedones and inflammatory lesions such as papules and nodules. A physical may be followed up next with particular attention paid to signs of an endocrine disorder including normal growth and weight, testicular growth, breast development, hirsutism or growth of pubic hair. Hormonal workup may not be necessary unless one of these abnormalities is present, then work up of testosterone, DHEA, DHEAS, LH and FSH or referral to a pediatric endocrinologist specialist may be recommended.