Journal of the American Academy of Dermatology
Hydroxychloroquine is effective therapy for control of cutaneous sarcoidal granulomas*
Cutaneous sarcoidosis often responds poorly to topical and intralesional corticosteroids but may respond to moderate to high doses of oral corticosteroids. To avoid the use of systemic corticosteroids, we treated 17 patients with cutaneous sarcoidal granulomas with hydroxychloroquine (2 to 3 mg/kg/day) in an open clinical trial. If response occurred, other medications were first tapered and then the hydroxychloroquine dosage was reduced or stopped. The cutaneous lesions of 12 patients regressed within 4 to 12 weeks, and they were able to stop other therapies; three patients had a partial response, and two patients had no regression. Two of eight patients with pulmonary sarcoidosis improved. No ocular toxicity was noted.
References (11)
- H Fuld
Sarcoidosis treated with chloroquine
Lancet
(1960) - SI Morse et al.
The treatment of sarcoidosis with chloroquine
Am J Med
(1961) - N Soderstrom
Two cases of sarcoidosis treated with mepacrine
Lancet
(1960) - PE Barre et al.
Hydroxychloroquine treatment of hypercalcemia in a patient with sarcoidosis undergoing hemodialysis
Am J Med
(1987) - TJ O’Leary et al.
The effects of chloro-quine on serum 1,25-dihydroxyvitamin D and calcium metabolism in sarcoidosis
N Engl J Med
(1986)
Cited by (162)
Cutaneous Sarcoidosis
2024, Clinics in Chest MedicineEfficacy and safety of mTOR inhibition in cutaneous sarcoidosis: a single-centre trial
2024, The Lancet RheumatologySarcoidosis is an inflammatory condition that can affect various organs and tissues, causing the formation of granulomas and subsequent functional impairment. The origin of sarcoidosis remains unknown and there are few treatment options. Mechanistic target of rapamycin (mTOR) activation is commonly seen in granulomas of patients across different tissues and has been shown to induce sarcoidosis-like granulomas in a mouse model. This study aimed to examine the efficacy and safety of the mTOR inhibitor sirolimus as a treatment for cutaneous sarcoidosis.
We did a single-centre, randomised study treating patients with persistent and glucocorticoid-refractory cutaneous sarcoidosis with sirolimus at the Vienna General Hospital, Medical University of Vienna (Vienna, Austria). We recruited participants who had persistent, active, and histologically proven cutaneous sarcoidosis. We used an n-of-1 crossover design in a placebo-controlled, double-blind topical treatment period and a subsequent single-arm systemic treatment phase for 4 months in the same participants. Participants initially received either 0·1% topical sirolimus in Vaseline or placebo (Vaseline alone), twice daily. After a washout period, all participants were subsequently administered a 6 mg loading dose followed by 2 mg sirolimus solution orally once daily, aiming to achieve serum concentrations of 6 ng/mL. The primary endpoint was change in the Cutaneous Sarcoidosis Activity and Morphology Index (CSAMI) after topical or systemic treatment. All participants were included in the safety analyses, and patients having completed the respective treatment period (topical treatment or systemic treatment) were included in the primary analyses. Adverse events were assessed at each study visit by clinicians and were categorised according to their correlation with the study drug, severity, seriousness, and expectedness. This study is registered with EudraCT (2017-004930-27) and is now closed.
16 participants with persistent cutaneous sarcoidosis were enrolled in the study between Sept 3, 2019, and June 15, 2021. Six (37%) of 16 participants were men, ten (63%) were women, and 15 (94%) were White. The median age of participants was 54 years (IQR 48–58). 14 participants were randomly assigned in the topical phase and 2 entered the systemic treatment phase directly. Daily topical treatment did not improve cutaneous lesions (effect estimate –1·213 [95% CI –2·505 to 0·079], p=0·066). Systemic treatment targeting trough serum concentrations of 6 ng/mL resulted in clinical and histological improvement of skin lesions in seven (70%) of ten participants (median –7·0 [95% CI –16·5 to –3·0], p=0·018). Various morphologies of cutaneous sarcoidosis, including papular, nodular, plaque, scar, and tattoo-associated sarcoidosis, responded to systemic sirolimus therapy with a long-lasting effect for more than 1 year after treatment had been stopped. There were no serious adverse events and no deaths.
Short-term treatment with systemic sirolimus might be an effective and safe treatment option for patients with persistent glucocorticoid-refractory sarcoidosis with a long-lasting disease-modulating effect. The effect of sirolimus in granulomatous inflammation should be investigated further in large, multi-centre, randomised clinical trials.
Vienna Science and Technology Fund, Austrian Science Fund.
Hydroxychloroquine: Key therapeutic advances and emerging nanotechnological landscape for cancer mitigation
2023, Chemico-Biological InteractionsHydroxychloroquine (HCQ) is a unique class of medications that has been widely utilized for the treatment of cancer. HCQ plays a dichotomous role by inhibiting autophagy induced by the tumor microenvironment (TME). Preclinical studies support the use of HCQ for anti-cancer therapy, especially in combination with conventional anti-cancer treatments since they sensitize tumor cells to drugs, potentiating the therapeutic activity. However, clinical evidence has suggested poor outcomes for HCQ due to various obstacles, including non-specific distribution, low aqueous solubility and low bioavailability at target sites, transport across tissue barriers, and retinal toxicity. These issues are addressable via the integration of HCQ with nanotechnology to produce HCQ-conjugated nanomedicines. This review aims to discuss the pharmacodynamic, pharmacokinetic and antitumor properties of HCQ. Furthermore, the antitumor performance of the nanoformulated HCQ is also reviewed thoroughly, aiming to serve as a guide for the HCQ-based enhanced treatment of cancers. The nanoencapsulation or nanoconjugation of HCQ with nanoassemblies appears to be a promising method for reducing the toxicity and improving the antitumor efficacy of HCQ.
Cutaneous Sarcoidosis
2023, Dermatologic ClinicsHydroxychloroquine for non-severe extra-pulmonary sarcoidosis
2022, Revue de Medecine InterneLa sarcoïdose peut évoluer vers une maladie chronique dans environ 30 % des cas. Lorsqu’un traitement général est indiqué, les corticoïdes constituent le traitement de première ligne. Plus d’un tiers des patients traités par corticoïdes reçoivent un agent d’épargne cortisonique. Bien que le méthotrexate soit l’agent d’épargne le plus souvent employé, les antipaludéens de synthèse sont utilisés depuis plus de cinquante ans sur la base d’essais thérapeutiques, randomisés, de faible taille. Malgré ce faible niveau de preuve, la chloroquine ou plus souvent désormais l’hydroxychloroquine sont utilisées en pratique quotidienne, notamment pour traiter les sarcoïdoses cutanée et articulaire, ainsi que l’hypercalcémie et certaines uvéites.
Cette revue synthétise l’état des connaissances sur le traitement d’épargne cortisonique dans la sarcoïdose, notamment dans sa forme extra-pulmonaire. Ces données étayent la nécessité de conduire des essais thérapeutiques de bonne qualité pour valider l’utilisation de l’hydroxychloroquine dans cette indication spécifique.
Sarcoidosis can develop into a chronic disease in about 30% of cases. When general treatment is indicated, corticosteroids are the first-line treatment. More than one third of patients treated with corticosteroids receive a steroid-sparing agent. Although methotrexate is the most commonly used sparing agent, synthetic antimalarials have been used for more than fifty years on the basis of small, randomised, therapeutic trials. Despite this low level of evidence, chloroquine or more often hydroxychloroquine are used in daily practice, particularly to treat skin, bone and joint sarcoidosis, as well as hypercalcemia and certain types of uveitis.
This review summarises the state of knowledge on steroid-sparing therapy in sarcoidosis, particularly in its extra-pulmonary form. These data support the need for good quality therapeutic trials to validate the use of hydroxychloroquine in this specific indication.
Hydroxychloroquine: An Essential Drug in Dermatology and Its Controversial Use in COVID-19
2022, Actas Dermo-SifiliograficasLa hidroxicloroquina es un antimalárico con acción inmunomoduladora, antiinflamatoria, antibacteriana y antiviral. Posee un buen perfil de seguridad y puede ser utilizada en niños, en mujeres embarazadas o durante la lactancia, y no produce inmunosupresión. La retinopatía es uno de sus efectos adversos más temidos y requiere controles regulares. La hidroxicloroquina es un fármaco esencial en dermatología, utilizado ampliamente con buenas tasas de respuesta clínica tanto como un tratamiento de primera línea en el lupus eritematoso, como en múltiples dermatosis autoinmunes/inflamatorias como liquen plano, erupción polimorfa lumínica, porfiria cutánea tarda, granuloma anular y sarcoidosis, entre otras. Durante el año 2020 fue prescrita a gran escala como profilaxis y tratamiento de la infección producida por el coronavirus SARS-CoV-2 (COVID-19). El aumento de la utilización de hidroxicloroquina produjo serias dificultades para su obtención e incluso desabastecimiento. En metaanálisis recientes se ha concluido que la hidroxicloroquina no es efectiva para el tratamiento de esta patología y se desaconseja su prescripción.
Hydroxychloroquine is an antimalarial drug with immunomodulatory, anti-inflammatory, antibacterial, and antiviral properties. It has a good safety profile, can be used in children and in pregnant and breastfeeding women, and does not suppress the immune system. Regular screening for retinopathy, one of the drug's most feared adverse effects, is necessary. Hydroxychloroquine is a widely used, essential drug in dermatology. Clinical response rates are good in lupus erythematous, where it is a first-line therapy, as well in numerous autoimmune/inflammatory diseases, including lichen planus, polymorphic light eruption, porphyria cutanea tarda, granuloma annulare, and sarcoidosis. In 2020, it was widely prescribed both to prevent and to treat COVID-19 caused by SARS-CoV-2. Its increased use led to serious supply shortages and in some cases stocks were entirely depleted. Recent meta-analyses have concluded that hydroxychloroquine is ineffective against COVID-19 and have advised against its use.
- *
Presented in part at the American Academy of Dermatology's summer session, Chicago, Ill., April 19, 1984.