Embryology, Lanugo

Development

Lanugo plays an essential role in binding the vernix caseosa to the skin of fetuses. Vernix caseosa is the viscous white covering on newborns that protects their skin, prevents water loss, plays an important role in thermoregulation, and contributes to innate immunity. It protects the fetus from damaging substances found in amniotic fluid, most notably urea and electrolytes.[1] Lanugo is the first type of hair to develop in humans. The interaction of lanugo with the vernix is also important in controlling the tempo of the fetal developmental rate during various times in the gestation cycle. Lanugo arises about 3 months into development. Hair growth starts on the scalp around the eyebrow, nose, and forehead area and proceeds in a cephalocaudal direction from head to toe. It is shed at about 33 to 36 weeks gestation, when it becomes incorporated into the amniotic fluid, eventually contributing to the composition of the meconium. Lanugo is ultimately replaced by vellus (fine, thin hair) and terminal hair (thicker hairs found on the scalp, axilla, and genitalia). Lanugo often remains present in 30% of newborns; this is a normal finding.

After removal of the vernix, small amounts of lanugo can temporarily remain on the neonate. Lanugo can thus be present in the neonate for the first few weeks of life. Its presence can, however, indicate premature birth in a minority of cases. When present in an adult, lanugo can indicate serious underlying disease states. These include, most notably, anorexia nervosa, bulimia nervosa, various forms of malnutrition, and the presence of a teratoma.[2]

Cellular

Lanugo, like all types of hair, is derived from the ectoderm. The cell types present in the hair follicle of lanugo hair include hair follicle stem cells (present in the bulge and matrix of the hair follicle), germinal matrix cells (form the hair shaft), mesenchymal cells (form the hair papilla), keratinocytes (form keratin in the epidermis), and fibroblasts (form collagen). While about 20 different cell types comprise the hair follicle of a lanugo hair, the cells mentioned above are the most relevant to clinical practice.

Biochemical

To form lanugo hair, many biochemical processes involving signal relays from the dermal papilla to the hair follicle occur. These processes result in the activation of downstream signaling pathways and transcription factors. These pathways include but are not limited to, Wnt, sonic hedgehog, notch, ectodysplasin A, and bone morphogenetic protein.

Molecular Level

The sonic hedgehog (Shh) pathway and its effectors are key to lanugo development and the development of other hair types. Antagonists of Wnt and its effectors are also crucial. While other mediators are necessary for the eventual production of lanugo, these 2 are the most important. In either case, molecular messages initiating the hair development process begin in the dermis.[3] Without a Wnt signal, cytoplasmic β-catenin is phosphorylated and targeted for destruction by a protein complex. This complex includes axin, adenomatous polyposis coli tumor suppressor protein (APC), and glycogen synthase 3-β (GSK3-β).

In the presence of an antagonistic Wnt signal, there is inhibition of the degradation complex, and β-catenin moves to the nucleus. There, it forms a transcription complex with DNA binding factors of the lymphoid enhancer-binding factor/T cell factor family. This complex then activates the transcription of various target genes. In the absence of an Shh signal, the actions of the patched-1 (PTC1) Shh receptor inhibit the activity of the smoothened (SMO) protein. In the presence of Shh, the repression of SMO is removed, and target genes, including PTC1 and GLI1, are transcribed through the actions of the transcription factors GLI1 and GLI2. After further downstream processes, lanugo and other types of hair formation occur.[4]

Function

Lanugo plays a vital role in binding the vernix to the skin, protecting the fetus from damaging substances found in amniotic fluid. Lanugo’s interaction with the vernix also results in an increased rate of fetal growth during mid-gestation and a decreased rate at the end of gestation.

Mechanism

Lanugo fulfills its role as a physical anchor between the skin and vernix. Lanugo imparts an increased surface area to the fetus, allowing more interactions between itself and the vernix, strengthening the anchor. Without lanugo, the vernix would not remain affixed to the skin and, therefore, would be unable to protect the fetus from harmful environmental substances.[5]

When regulating fetal developmental rate, oscillations of lanugo hairs surrounded by the vernix during fetal movements in amniotic fluid activate sensitive mechanoreceptors connected to unmyelinated C-afferent fibers. These afferents relay impulses from all fetal skin dermatomes via the spinal cord and activate the vagal sensory zone, hypothalamus, and insular cortex. This process promotes an "anti-stress" effect through oxytocin release, which also stimulates fetal growth by the incretin effect of various gastrointestinal hormones.

Testing

Lanugo is detectable on a physical exam, and it is fine, thin, soft, and depigmented hair. If the suspicion is that lanugo is due to other diseases, a more thorough systemic workup is necessary. This assessment includes psychiatric evaluation for anorexia and bulimia nervosa, complete blood count, complete metabolic panel, and the search for other tumor markers indicative of a teratoma. The clinician should note the degree of lanugo presence and its distribution, which can correlate with disease severity.

Pathophysiology

In disease states such as malnutrition and anorexia nervosa, where thermoregulation becomes disrupted, lanugo grows to help insulate the body. This growth is a natural response to an unnatural insult. Molecular signals from the dermal papilla are released following the detection of temperature dysregulation and cause a series of signaling events (primarily via SMO, PTCH, and other Shh components), leading to the formation of lanugo hair.

Clinical Significance

If the clinician recognizes the presence of lanugo in a newborn, it should raise suspicion for prematurity; however, this is more often a normal variant than not. When lanugo is present in an adult, this is a "red flag," an underlying systemic disease that should be investigated and ruled out.