Perifollicular Fibrosis and Perifollicular Inflammation in Androgenetic Alopecia

Perifollicular Inflammation and Perifolliuclar Fibrosis are Part of Balding

It had long been though that male and female patterned hair loss (‘balding') is a relatively non-inflammatory process. The last decade has repeatedly shown that this is not the case and that inflammation is likely very much a part of the process and likely contributes in some way to the balding process itself.

The current model of AGA suggests that ‘micro inflammation’ in AGA might trigger apoptosis and perifollicular fibrosis which in turn causes hairs to miniaturize and shed.

Inflammation in AGA: How common is it anyways?

Inflammation is commonly seen in androgenetic alopecia and is likely part of the condition itself. Studies by Whiting showed that perifollicular inflammation was present in 40 % of AGA biopsies. The inflammation present in AGA is different than the inflammation seen in the destructive scarring alopecias like lichen planopilaris. In 2000, Mahe used the term “microinflammation” to describe this types of inflammatory process.

Inflammation in AGA: Where is it found?

Inflammation in AGA is mainly seen in the upper parts of the hair follicle. Inflammation is commonly found in both the isthmus and isthmus which are the upper portions of the hair follicle. Minor amounts of inflammation around hair follicles can be seen in the normal scalp as well in in androgenetic alopecia. However, more marked degrees of inflammation are not normally seen in the scalp but can be a feature of androgenetic alopecia. Ramos in 2016 showed that inflammation is more common around miniaturizing hairs and this inflammation seems to be associated with a form of cell death known as apoptosis. In 1992, Jaworsky and colleagues showed that biopsies of males and females with androgenetic alopecia showed the presence of activated T-cell infiltrates about the lower portions of follicular infundibula. Inflammatory cells infiltrated the region of the follicular bulge, the putative source of stem cells in cycling follicles. It was postulated that the progressive fibrosis of the perifollicular sheath might begin with T-cell infiltration of follicular stem cell epithelium and that the perifollicular fibrosis actually impairs hair growth.

Cell death (Apoptosis) is AGA: Where does it occur?

Cell death via programmed cell death or ‘apoptosis. is also very much a part of AGA. It is known that apoptosis is dermal papilla cells is important in AGA and is proposed to reduce the cell mass of the dermal papilla and in turn lead to miniaturization.

In 2010, El-Domyati and colleagues showed that apoptosis (by bcl-2 immunostaining) was present in both the dermal papilla and in perifollicular lymphocytes (i.e. the white blood cells that comprise the perifollicular inflammation). The authors showed that the apoptosis in dermal papilla cells was associated with reduced cell activity and cell division (as measured by proliferating cell nuclear antigen staining PCNA).

Can we detect how much inflammation is present in AGA without a biopsy?

To date, there is no better way to detect inflammation than a biopsy. Of course, biopsies are seldom done in AGA because the diagnosis is largely clinical. However, careful examination of the scalp with dermosocpy may help pinpoint inflammation occurring beneath the scalp. In 2004, Deloche showed that peripilar signs (PPS) by dermoscopy were correlated with the presence of inflammation beneath the scalp.

Does inflammation and fibrosis really matter?

The inflammation and fibrosis seen in androgenetic alopecia probably does matter. The inflammation likely triggers abnormalities in how hair cycles (i.e. telogen effluvium) and likely contributes to the progressive ‘miniaturization’ of hairs over time.

Perifollicular inflammation in AGA appears to occur very early in the condition. In 2009, El-Domyati showed the perifollicular inflammation was present early the condition long before perifollicular fibrosis started to be seen. Over time, as perifollicular fibrosis became more commonly seen as perifollicular inflammation started to decrease. In other words, the two phenomena seemed to have an inverse correlation. Gonzalez showed in 2010 that perifollicular fibrosis was even a common findings in androgenetic alopecia occurring in teenagers.

Perfifollicular inflammation and fibrous probably affect how hairs grow. In 1993, Whiting performed some classic studies that have shaped how we think about inflammation in AGA. He showed that patients with perifollicular inflammation and fibrosis have poorer responses to minoxidil. Individuals with moderate or dense lymphocytic inflammation and perifollicular fibrosis may have poorer responses to minoxidil.

What causes the perifollicular fibrosis anyways?

It’s not entirely clear what causes the perifollicular fibrosis to occur. In 2006, Yoo and colleagues proposed that TGF-beta (transforming growth factor beta) seemed to play a role. They showed that testosterone treatment increased the expression of type I procollagen at mRNA and protein level and this was associated with a rise in TGF-beta protein levels by 81.9 % in dermal fibroblasts. Conversely, pretreatment of finasteride inhibited the ability of testosterone to make pro collagen RNA and protein and decreased the expression of TGF-bet by 30 %. Interestingly, pretreatment of follicles with a TGF-beta antibody inhibited pro collagen expression leading the authors of the study to conclude that testosterone triggers TGF-beta expression and perfiollciular fibrosis in AGA. They also postulate that one mechanisms of finasteride may be to reduce TGF-beta and therefore pro collagen expression.


Androgenetic alopecia is no longer viewed as a “non-inflammatory” condition. Inflammation is very much a part of AGA and this inflammation likely drives the development of perifollicular fibrosis and an inflammatory millieu that drives the apoptosis of dermal papilla cells and therefore the progression miniaturization of hair follicles.

So, do we need to treat the inflammation? That answer is ‘probably’ - it’s just we don’t quite know how to best do this yet. There are many different types of anti-inflammatory treatment including corticosteroids, doxycycline, tacrolimus, TNF-inhibitors, immunomodulatory and immunosuppressants. It’s a bit of a guess as to how best to address the inflammation in AGA and more research is needed. It’s extremely likely this will play a beneficial role, particularly the earlier such anti-inflammatory treatment is started. Treatment will likely be needed over an extended period rather than for a few days or weeks.


Deloche C, et al. Histological features of peripilar signs associated with androgenetic alopecia. Arch Dermatol Res. 2004.

El-Domyati M, et al. Androgenetic alopecia in males: a histopathological and ultrastructural study.. J Cosmet Dermatol. 2009.

El-Domyati M, et al. Evaluation of apoptosis regulatory markers in androgenetic alopecia. J Cosmet Dermatol. 2010.

Gonzalez ME, et al. Androgenetic alopecia in the paediatric population: a retrospective review of 57 patients. Br J Dermatol. 2010.

Jaworsky C, et al. Characterization of inflammatory infiltrates in male pattern alopecia: implications for pathogenesis. Br J Dermatol. 1992.

Mahé YF, et al. Androgenetic alopecia and microinflammation. Int J Dermatol. 2000.

Nirmal B, et al. Evaluation of Perifollicular Inflammation of Donor Area during Hair Transplantation in Androgenetic Alopecia and its Comparison with Controls. Int J Trichology. 2013.

Ramos PM, et al. Apoptosis in follicles of individuals with female pattern hair loss is associated with perifollicular microinflammation. Int J Cosmet Sci. 2016.

Whiting DA. Diagnostic and predictive value of horizontal sections of scalp biopsy specimens in male pattern androgenetic alopecia. J Am Acad Dermatol. 1993.

Yoo HG, et al. Perifollicular fibrosis: pathogenetic role in androgenetic alopecia. Biol Pharm Bull. 2006.

Dr. Jeff Donovan is a Canadian and US board certified dermatologist specializing exclusively in hair loss. To schedule a consultation, please call the Whistler office at 604.283.1887

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