Table 9.

Summary of effective systemic therapies in recalcitrant lichen sclerosus (170–181).

Drugs	Dosis	Efficacy	Side effects	Grade of recommendation	Level of evidence
Pulsed steroid and methotrexate	Methylprednisolone 1,000 mg/d IV for three days monthly + methotrexate 15 mg/w PO > 6 months	Decrease of the clinical score after 3 months of treatment in 85,7% of patients	Methylprednisolone: hypertension, arrhythmia, hyperglycemia, hypokalemia, abnormal behavior, risk of infections.	3	D
Retinoids	Acitretin 20–30 mg/d PO 16 weeks Etretinate 1 mg/kg/d PO 14–18 weeks	Acitretin efficacy group 64 vs. 25% placebo group Etretinate: Improvement of symptoms in 75% of patients.	Cheilitis and dry skin (+++), palmoplantar peeling, hepatic alterations, hypertriglyceridemia, abdominal pain, dizziness, hair loss, teratogenesis.	1+	B
Ciclosporin	3–4 mg/kg/d PO for 3 months	Decrease of the clinical score after 1 month and symptoms after 3 months in five patients.	Nausea, hypertrichosis, mucositis	3	D
Methotrexate	10–15 mg/w PO 6 months	Clinical improvement in 75% of patients after a median of 3 months	MethotrexateNausea, headache, increase of liver enzyme levels; Gastrointestinal discomfort, fatigue, hair loss.	3	D
Hydroxycarbamide	1 g/d PO 1 month	Improvement of symptoms in a single case report.	Gastrointestinal discomfort neutropenia, Carcinogenicity	3	D
Hydroxychloroquine	200 mg/d PO 3 months	Case report with resolution of the symptoms and modest clinical improvement	Nausea, diarrhea, skin rash, retinopathy, hemolytic anemia,	3	D
Antibiotics	Penicillin G benzathine 2.4 M units IM or Ceftriaxone 1 g IM every 2 weeks, next once a month	A 53,3% disease clearing with or without residual atrophy, after 3 to 9 months.	Injection site pain, type I hypersensitivity reactions, C. difficile-associated diarrhea	3	D
Sulphasalazine	1–2 g/d PO (long-term therapy)	Case report. Reduction of the skin infiltration after 1 month	Headache, nausea, fever, skin rash, and reversible infertility in men, pancreatitis.	3	D
Vitamin D	Calcitriol 0.5 μg/d PO 6 months	Case report with clinical and histological improvement after 4–6 months	Hypercalciuria	3	D
Baricitinib	2 mg/d PO combined with PUVA twice-weekly	Case report in eLS with improvement of pigmentation and atrophy after three months	Not described in this case report.	3	D

Grade recommendations and levels of evidence are explained in Supplementary Table 1.