# Repurposing Historic Drugs for Neutrophil-Mediated Inflammation in Skin Disorders
## 4 Tetracyclines
### Granulomatous Diseases  
Tetracyclines have been shown to inhibit granuloma formation in vitro, and minocycline has demonstrated the ability to inhibit T cell proliferation in vitro, while incyclinide, a chemically modified doxycycline lacking antibiotic activity but possessing enhanced anti-inflammatory properties, has shown potential in suppressing MMPs and may represent a promising treatment for granulomatous diseases [90]. [PERSON] et al. reported six cases of treatment-resistant GA that resolved after three months of therapy with a combination of rifamp at 600 mg, ofloxacin at 400 mg, and minocycline hydrochloride at 100 mg administered monthly. The complete clearance of the plaque occurred within 3 to 5 months, though some patients experienced post-inflammatory hyperpigmentation [91]. [PERSON] et al. described a case of multi-resistant GGA that showed near-complete resolution after a 10-week course of doxycycline at 100 mg/day, with sustained improvement for over a year [92]. The use of tetracyclines in multi-resistant GA is noteworthy and may offer a low-toxicity alternative to first-line topical corticosteroid therapy.  
Tetracycline derivatives, due to their favorable safety profile, have emerged as valuable treatments for extensive cutaneous sarcoidosis and may be combined with topical and intralesional corticosteroids. Although data are mainly derived from open, nonrandomized trials, minocycline has shown promising results, achieving complete responses in up to two-thirds of cases [93]. Tetracyclines help manage the extensive cutaneous manifestations of sarcoidosis through their anti-inflammatory and immunomodulatory effects, particularly on T cells. Some evidence supports the involvement of anti-infectious mechanisms in tetracycline's efficacy in sarcoidosis. Recent studies have identified DNA specific to mycobacteria and _Propionibacterium acne_ in sarcoidal lymph nodes, with the latter being known for its sensitivity to tetracyclines. In a retrospective study by [PERSON] et al., minocycline appeared to be a promising option for treating moderate cutaneous sarcoidosis, with 74% of patients (20 out of 27) responding to therapy. Based on the current literature, the authors recommend a stepwise therapeutic approach, with minocycline as the first-line therapy, followed by hydroxychloroquine, methotrexate, thalidomide, and biological agents [94]. Tetracyclines may represent an important therapeutic tool even in cases of sarcoidosis affecting special sites. One case involved a 45-year-old woman with a 7-year history of subcutaneous nodular sarcoidosis and new-onset dyspnea. Although initially treated with corticosteroids, her disease recurred upon withdrawal. A 6-month course of doxycycline at 200 mg/day led to complete remission, underscoring the importance of systemic evaluation and regular monitoring in such cases [95]. Similarly, in tattoo-associated sarcoidosis, a patient achieved the complete clearance of skin lesions and normalization of chest X-ray findings after 4 months of treatment with a mid-potency topical steroid and doxycycline [96].  
The immunomodulatory and anti-infectious properties of minocycline have been suggested to explain its efficacy in inflammatory diseases beyond sarcoidosis, such as rheumatoid arthritis. Tetracyclines should also be considered an alternative therapy in cases that show the resistance of sarcoidosis lesions to antimalarial drugs [97].  
Tetracyclines have been used to treat ulcerated NL, often in combination with topical corticosteroids or tacrolimus, to promote ulcer healing. [PERSON] et al. reported a case where doxycycline significantly improved ulcerated NL, likely due to its anti-inflective, anti-inflammatory, and immunomodulatory properties [81].