Part 2
Dear readers, in this article, we cover sections 2, 3, and 4.
Alopecia Areata
In the case of AA, therapeutic advances can be summarized into two groups:
a) New data and methods of using traditional treatments, and
b) New therapies.
a) In the first group, a review by Lamb et al.⁴⁶ on the use of immunotherapy with diphencyprone in 133 patients with AA observed some type of response in 72% of patients, with more than 90% regrowth in 16%. Another significant development in this group concerns the pulsatile administration of systemic corticosteroids for AA. There is evidence of greater safety and at least the same effectiveness when using corticosteroids in pulse form⁴⁷,⁴⁸. A study conducted by the research group at Hospital Ramón y Cajal in Madrid⁴⁸ found that oral dexamethasone at a dose of 0.1 mg/kg/day for two consecutive days per week induced regrowth in 25 out of 31 patients with total or universal AA (Fig. 2), with mild adverse effects in 32%.
b) In the second group of new therapies, the possible usefulness of the combination of simvastatin-ezetimibe for AA due to its immunomodulatory effect stands out. A study showed that 14 out of 19 patients with extensive AA responded to this treatment⁴⁹. However, other authors have reported significantly lower response rates (1 out of 20 patients)⁵⁰. The combination of simvastatin and ezetimibe could serve as an adjunctive therapy to enhance response when used alongside other treatments, but its effectiveness as monotherapy appears to be very limited.
The most significant breakthrough in the field of AA—and one of the most important in trichology in recent years—is the therapeutic utility of Janus kinase inhibitors (JAK inhibitors)⁵¹-⁵⁸. Their importance lies not only in their apparent effectiveness but also in the fact that they represent the first treatment targeting a specific pathogenic mechanism in AA. The JAK pathway plays a role in activating cytotoxic CD8 T lymphocytes and producing interferon-gamma, key agents in AA development. Inhibiting this pathway appears to induce regrowth in affected patients. The JAK inhibitors showing potential utility for AA include tofacitinib⁵⁵-⁵⁸ (currently approved for rheumatoid arthritis), ruxolitinib⁵¹,⁵²,⁵⁴ (approved for myelofibrosis and polycythemia vera), and baricitinib⁵³ (awaiting approval for rheumatoid arthritis). These oral medications have an acceptable safety profile.
Additionally, the first study on the utility of topical ruxolitinib for eyebrow AA has been published⁵², and clinical trials are underway for new topical JAK inhibitors such as LEO-124249 (NCT02561585). The primary limitation of these treatments is cost. Nonetheless, they open a new avenue for therapeutic research in AA.
Scarring Alopecias
Regarding frontal fibrosing alopecia (FFA), the current interpretation of its pathogenesis suggests a dual autoimmune and hormonal mechanism⁵⁹-⁶¹. This justifies the use of anti-inflammatory treatments (corticosteroids) to counteract autoimmune inflammation, along with antiandrogenic drugs (finasteride and dutasteride). In recent years, several studies⁵⁹-⁶⁴ have highlighted the potential utility of these drugs for FFA, including a Spanish multicenter study involving 355 patients⁵⁹. The precise mechanism by which antiandrogens act in FFA remains unclear, but it appears that inhibiting the action of male hormones on the hair follicle root helps stabilize the disease⁵⁹,⁶¹. Some studies have even demonstrated hair regrowth with the administration of antiandrogens⁶⁴. However, some authors remain skeptical about their use in FFA⁶⁵. Despite the undefined exact mechanism, there is evidence supporting a hormonal factor in FFA⁶¹.
Another major therapeutic advance in FFA and lichen planopilaris (LPP) is the use of the oral antidiabetic drug pioglitazone due to its agonist effect on peroxisome proliferator-activated receptors (PPAR-gamma). Recent studies⁶⁶ suggest that PPAR-gamma dysfunction may play a role in triggering inflammation in LPP and FFA. Four studies⁶⁷-⁷⁰ have explored the use of pioglitazone for treating LPP and FFA, with variable results—effectiveness ranging from 20% to 70% and side effects occurring in up to 50% of patients. Márquez and Camacho⁷¹ conducted a study on 68 women with FFA, reporting favorable results in 64% of cases using pioglitazone. The authors believe that pioglitazone may be effective in some cases, but its use carries a considerable risk of intolerance, primarily due to lower limb edema and weight gain, which often lead to treatment discontinuation.
In the case of folliculitis decalvans (FD), a Spanish multicenter study involving 82 patients⁷² concluded that the most effective treatment—leading to improvement in 15 out of 15 treated patients and the longest post-treatment remission period (7.2 months)—was the combination of rifampicin and clindamycin for 10 weeks (Fig. 3). Another therapeutic advancement has been the reported potential benefit of photodynamic therapy (PDT) in 9 out of 10 FD patients⁷³. However, other authors have reported negative experiences with PDT in 3 out of 3 patients⁷⁴.
Hair Transplantation
Finally, in the field of hair transplantation, two major advancements stand out. First, the introduction of new robotic and automated systems, which improve surgical speed and, in some cases, reduce follicular transection rates in the follicular unit extraction (FUE) technique⁷⁵. However, it is important to note that achieving the best results depends more on the surgeon’s skill than on the device used.
The second notable advancement is a new follicular extraction technique known as “partial longitudinal extraction”. This method involves partially extracting follicular units so that the portion of the follicle remaining in the donor area can survive and regenerate a complete follicular unit. This approach aims to prevent the progressive depletion of the donor area. While this is an interesting concept, it remains under development.
Conclusions
In recent years, we have witnessed significant advancements in trichological therapy. More importantly, new lines of research have emerged, paving the way for further progress. The developments discussed in this article, covering the past three years, represent more than just hope—they are a reality.
