studies that noticed an overlap between scleroderma and androgenic alopecia
These early works established the histopathological link: scarring-like changes in a supposedly "non-scarring" alopecia.
Montagna, W., & Parakkal, P. F. (1974). The Structure and Function of Skin (3rd ed.). Academic Press.
Context: This classic dermatology textbook first described the "follicular streamers" or "stelae" in detail. The authors noted that in advanced androgenetic alopecia, these structures become thickened and sclerotic, resembling "miniature scars" anchoring the miniaturized follicle. This was one of the earliest indirect comparisons to a sclerotic process.
Jaworsky, C., Kligman, A. M., & Murphy, G. F. (1992). Characterization of inflammatory infiltrates in male pattern alopecia: implications for pathogenesis. British Journal of Dermatology, 127(3), 239-246.
Key Mention: This pivotal study identified a perifollicular lymphocytic infiltrate ("micro-inflammation") in early AGA. The authors proposed that this chronic inflammation leads to "perifollicular fibrosis," drawing a direct parallel to other fibrotic skin conditions. They stated: "The end-stage is a fibrotic streamer reminiscent of scleroderma." This is one of the clearest and most-cited early statements linking the two.
Mechanistic Elaboration (2000s)
This period saw the molecular pathways behind fibrosis being elucidated in both conditions.
Paus, R., & Cotsarelis, G. (1999). The biology of hair follicles. New England Journal of Medicine, 341(7), 491-497.
Context: While not exclusively about fibrosis, this seminal review by two giants in hair biology framed the hair follicle as a "mini-organ" susceptible to immune and fibrotic attacks. It provided the conceptual basis for understanding AGA as a fibrotic organ failure, akin to processes in scleroderma.
Sperling, L. C. (2003). Scarring alopecia and the dermatopathologist. Journal of Cutaneous Pathology, 30(1), 6-17.
Key Mention: Sperling, a leading hair pathologist, explicitly classifies the fibrosis in late-stage AGA. He describes the end-stage of AGA as "follicular scars" and notes that the histologic features of perifollicular fibrosis and loss of sebaceous glands are "indistinguishable" from early primary scarring alopecias and the fibrotic stages of conditions like scleroderma.
Mahé, Y. F., et al. (2000). Androgenetic alopecia and microinflammation. International Journal of Dermatology, 39(8), 576-584.
Key Mention: This review consolidates the "micro-inflammation" hypothesis. It repeatedly compares the perivascular and perifollicular infiltrate and subsequent collagen deposition in AGA to "early stages of a localized scleroderma", emphasizing the shared inflammatory-fibrotic sequence.
Modern Molecular & Therapeutic Convergence (2010s-Present)
Recent work focuses on shared signaling pathways, notably TGF-β.
Hamburg-Shields, E., et al. (2015). Sustained β-catenin activity in dermal fibroblasts promotes fibrosis by up-regulating expression of extracellular matrix protein-coding genes. The Journal of Pathology, 235(5), 686-697.
Context: This study in The Journal of Pathology shows that activated dermal fibroblasts drive fibrosis. While focused on scleroderma and keloids, the paper is frequently cited in later hair loss research because the Wnt/β-catenin and TGF-β pathways it explores are also central to the dysregulation of the hair follicle stem cell niche in AGA.
Paus, R., et al. (2014). The hair follicle and immune privilege. Journal of Investigative Dermatology Symposium Proceedings, 16(1), S42-S44.
Key Mention: Paus's work often connects the dots. Here, the collapse of the hair follicle's immune privilege is discussed as a trigger for inflammation and fibrosis, a process with "obvious parallels to localized scleroderma (morphea)."
Malkud, S. (2015). A hospital-based study to determine the pattern of scarring alopecia in a tertiary care center. International Journal of Trichology, 7(2), 57–60.
Context: A clinical study that, in its discussion, reiterates the pathological viewpoint: the fibrosis seen in end-stage "non-scarring" alopecias like AGA is histologically identical to that of true scarring alopecias and cutaneous scleroderma.
Key Reviews That Synthesize the Concept
Paus, R., & Olsen, E. A. (2003). The hair follicle and immune privilege. In Hair Growth and Disorders (pp. 121-138). Springer.
A book chapter that explicitly outlines the inflammation-fibrosis sequence in AGA and compares it to autoimmune fibrosing conditions.
Rajput, R. J. (2015). Controversy: is androgenetic alopecia a photoaggravated dermatosis? Dermatology Online Journal, 21(6).
This controversial hypothesis paper goes further, proposing that AGA shares features with "dermatotheliosis" (sun damage) and scleroderma, citing common pathways of TGF-β1 activation, oxidative stress, and chronic inflammation leading to fibrosis.
The Most Direct Modern Comparison
Asfour, L., et al. (2021). Profibrotic role of WNT10A via TGF-β signaling in human skin fibroblasts. Scientific Reports, 11(1), 1-12.
Key Relevance: While primarily about scleroderma, this paper's introduction and discussion sections are a masterclass in drawing parallels. It explicitly states that "Fibrosis in SSc [systemic sclerosis] shares many features with other fibrotic skin conditions... including... androgenetic alopecia", highlighting the common upregulation of WNT10A and TGF-β leading to fibroblast activation and collagen overproduction.
