Hair loss frequently associated with autoimmunity

Hair loss (alopecia) has a number of possible contributing causes including low iron (measured by serum ferritin) and hypothyroid, but it frequently occurs due to autoimmune inflammation. This may be hard to recognize when instead of a full-blown autoimmune disease there are diffuse autoimmune inflammatory phenomena that are a milder forerunner known as Undifferentiated connective tissue disease (UCTD). A paper just published in the Italian Journal of Dermatology and Venereology discusses the importance of considering autoimmunity when investigating the causes of hair loss.

Hair loss can occur in various patterns

"Hair disorders are frequently observed in various systemic diseases, including autoimmune connective tissue diseases (CTDs), with predilection of lupus erythematosus (LE), followed by dermatomyositis (DM) and scleroderma. Hair disorders in CTDs may manifest as various clinical patterns, such as telogen hair loss, diffuse thinning or fragility of hair, and scarring alopecia. Less common hair disorders include anagen effluvium, alopecia areata, and trichomegaly. Some drugs used to treat CTDs may cause hair loss in a drug-related manner or hyperthrichosis."

The signs of common autoimmune connective tissue disorders often include hair loss:

"In the assessment of common hair loss patterns, such as telogen effluvium, the possible association with CTDs must be borne in mind and should not be overlooked. Alopecia appears to be a significant sign in the course of LE and especially systemic LE. In DM, the involvement of the scalp is common, and is often characterized by a diffuse, violaceous, scaly, non-scarring and symptomatic hair loss...The most important variant of scarring alopecia in the context of CTDs is that associated with discoid lupus erythematosus (DLE). In the diagnostic work-up of DLE-related cicatrical alopecia, histopathological and immunopathological studies are useful, and a relevant role has been attributed to dermatoscopy (trichoscopy) over the last years. Hair loss has been reported in several other CTDs, including mixed and undifferentiated CTDs, and primary Sjögren's syndrome, although it is likely to be underestimated in such diseases."

Undifferentiated connective tissue disease

Undifferentiated connective tissue disease is an extremely important clinical topic because this precursor to more developed autoimmune diseases likely accounts for a high percentage of human aches, pains and numerous other symptoms including hair loss. A paper just published in Clinical Reviews in Allergy & Immunology defines the pattern of cytokine imbalance often seen in UCTDs:

"Undifferentiated connective tissue disease (UCTD) is a unique clinical entity, a potential forerunner of well-established systemic autoimmune/rheumatic diseases. UCTD is characterized by the presence of various clinical symptoms, as well as a diverse repertoire of autoantibodies, resembling systemic autoimmune diseases. Since approximately one third of these patients consequently transform into a full-blown systemic autoimmune/rheumatic disease, it is of major importance to assess pathogenic factors leading to this progression. In view of the fact that the serological and clinical picture of UCTD and systemic autoimmune diseases are very similar, it is assumed that analogous pathogenic factors perpetuate both disease entities."

Th17/Treg dominance

Typical of most autoimmune inflammatory disorders throughout the whole spectrum is an imbalance between proinflammatory Th17 and antiinflammatory Treg (regulatory) immune cells with their associated cytokines as described for UCTD:

"In systemic autoimmune conditions, a quantitative and qualitative impairment of regulatory T cells has been shown previously, and in parallel, a relative dominance of pro-inflammatory Th17 cells has been introduced. Moreover, the imbalance between regulatory and Th17 cells plays a pivotal role in the initiation and propagation of UCTD."

Th17/Treg dominance with its associated cytokine imbalance is of significant for both diagnosis and treatment:

"Additionally, we depict a cytokine imbalance, which give raise to a biased T cell homeostasis from the UCTD phase throughout the fully developed systemic autoimmune disease stage. The levels of interleukin (IL)-6, IL-12, IL-17, IL-23, and interferon (IFN)-γ were pathologically increased with a parallel reduction of IL-10. We believe that the assessment of Th17/Treg cell ratio, as well as the simultaneous quantitation of cytokines may give a useful diagnostic tool at the early UCTD stage to identify patients with a higher chance of consecutive disease progression toward serious systemic autoimmune diseases. Moreover, the early targeted immunomodulating therapy in these patients may decelerate, or even stop this progression, before the development of serious autoimmune conditions with organ damage."

An opportunity to prevent further harm

In this respect, identifying hair loss as associated with early immune system dysregulation not only permits proper treatment of the presenting complaint but becomes an opportunity to ward off progression to more debilitating autoimmune disease.Clinical note: Screening for UCTD is aided by a multiple antibody autoimmune screen.