Rosacea Classification and  Treatment: History
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Serap Maden

Rosacea is a common chronic inflammatory skin condition. It mainly affects the cheeks, nose, chin, and forehead, causing flushing or transient erythema, persistent erythema, phymatous changes, papules, pustules, and telangiectasias, and the eyes may also be affected by rosacea. Rosacea is more common in women than in men and can start at any age. Rosacea affects both fair-skinned and darker-skinned people. Physical changes in the face due to rosacea can cause embarrassment, leading to reduced quality of life and self-esteem. Rosacea has several triggers, and its pathogenesis involves multiple factors, which means there are several treatment options, and these options can be combined. A patient’s clinical findings and symptoms will help a doctor to diagnose and classify the condition. Treatment options may include lifestyle changes, topical medications, systemic antibiotics and light-based therapy. 

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1. Rosacea Classification

Diagnostic criteria for rosacea have been described as primary and secondary features. Primary features include flushing (transient erythema), non-transient erythema, papules and pustules, and telangiectasias. In addition, secondary features may include burning or stinging, plaques, a dry appearance, edema, ocular manifestations, peripheral location, and phymatous changes. The presence of ≥1 primary feature is diagnostic, whereas secondary features are not necessarily present [1].

1.1. Erythematotelangiectatic Rosacea (Subtype 1)

The main features of this subtype are non-transient flushing and central facial edema. Telengiectasia may be accompanied by primary features, but these are not essential. In addition, flushing may be seen over the entire face, sparing the periocular and perioral areas, and the ears, neck, and upper chest may be affected [2][3].

1.2. Papulopustular Rosacea (Subtype 2)

On the central face, there are transient papules and pustules in addition to the ETR features. These papules and pustules, together with the ETR features, give a characteristic presentation of the condition [2].

1.3. Phymatous Rosacea (Subtype 3)

The skin becomes thicker and rougher due to phymatous changes, which mainly affect the nose. Rhinophyma is caused by an overgrowth of sebaceous glands in the skin of the nose, resulting in the thickening of the skin and an enlargement of the pores. This makes the skin appear rougher and thicker than it would normally be. These features can be seen in any sebaceous region. Phymatous changes can also be caused by a long-term exposure to ultraviolet radiation, which can stimulate oil production in the skin and further contribute to skin thickening [2].

1.4. Ocular Rosacea (Subtype 4)

The diagnosis of ocular rosacea depends on the presence of one or more of the following symptoms and findings in a patient: a watery or bloodshot appearance (interpalpebral conjunctival hyperemia), a foreign body sensation, burning or stinging, dryness, itching, light sensitivity, blurred vision, telangiectasias of the conjunctiva and lid margin, or lid and periocular erythema. Blepharitis, conjunctivitis, and irregular lid margins may also occur. Chalasia and sties are also symptoms of ocular rosacea [1].

1.5. Granulomatous Rosacea (Variant)

Granulomatous rosacea is the only type of rosacea that does not have the features of the other rosacea subtypes. Typical findings in granulomatous rosacea are dense, yellow, brown, or red papules or nodules on the skin. These lesions may be large and scarring. Typically, lesions on the cheeks and periorificial areas may also occur on the phyma. The presence of other rosacea findings is not essential for the diagnosis of granulomatous rosacea [1].

1.6. Rosacea Fulminans (Variant)

Rosacea fulminans, also referred to as ‘pyoderma faciale’ or ‘rosacea conglobata’, is a rare disorder that is distinguished by the sudden appearance of inflamed papules, pustules, nodules, and cysts on the facial area [4]. Rosacea fulminans may have a potential association with both inflammatory bowel disease and pregnancy [5].

1.7. Neurogenic Rosacea (Subtype)

The etiopathogenesis of rosacea has revealed its association with neurovascular components, which have been elucidated in recent years [6]. The term ‘neurogenic rosacea’ refers to an uncommon form that typically presents as intense redness with burning sensations limited to the cheeks, which worsen with the exposure to heat and stress [7][8]. Clinically, patients have reported experiencing burning or tingling sensations, as well as occasional intense pain. Furthermore, certain patients may encounter exceedingly severe symptoms that are unresponsive to traditional medication therapies, whether taken orally or applied topically. For instance, flushing can cause a sensation of warmth and discomfort. This can evoke adverse connotations for numerous patients, resulting in erythrophobia and avoidant behaviors [7].

2. Rosacea Treatment

There are many treatment options for rosacea, as well as new emerging modalities for treatment. Avoiding trigger factors for rosacea can have a beneficial effect. In addition, the treatment approach should be based on the clinical type and severity of the disease (Table 1).
Table 1. Algorithm of treatment options for rosacea types.
Treatment
Options/Types of Rosacea		 Topical Systemic (Oral) Devices Injection Other Prevention
Erythematelengiectatic Rosacea
(subtype 1)		 -Alpha-2 adrenergic agonists (brimonidine, oxymetazoline) -Beta blockers -IPL *
-Lasers (Nd:YAG †, PDL ‡)
-PDT §		 -Botulinum toxin (intralesional)   -Sunscreen
-Skin care
Papulopustular Rosacea
(subtype 2)		 -Azelaic acid
-Ivermectin
-Metronidazole
-Minocycline		 -Tetracyclines
-Macrolide
-Isotretinoin
-Metronidazole
-H. pylori eradication		 -Lasers (Nd:YAG)
-IPL
-PDT		     -Sunscreen
-Skin care
Phymatous Rosacea
(subtype 3)		 -Topical retinoids -Doxycycline
-Isotretinoin		 -Lasers (CO2 Laser) **   -Surgery -Sunscreen
-Skin care
Ocular Rosacea
(subtype 4)		 -Topical antibiotics
-Topical steroids
-Cyclosporin ophthalmic solution
-Warm compresses
-Eyelid scrubbing
-Preservative-free artificial tears		 -Omega-3 fatty acids
-Doxycycline
-Macrolide		     -Surgery -Sunscreen
-Skin care
Granulomatous Rosacea
(variant)		 -Azelaic acid
-Ivermectin
-Pimecrolimus		 -Tetracyclines
-Macrolide
-İsotretinoin
-Metronidazole
-Dapsone
-Steroids		 -Chromophore gel-assisted phototherapy
-IPL		     -Sunscreen
-Skin care
Rosacea Fulminans
(variant)		   -İsotretinoin
-Steroids		       -Sunscreen
-Skin care
Neurogenic Rosacea
(subtype)		   - Beta blockers
-Neuropathic pain medication (gabapentin, pregabalin)
-Antidepressants (duloxetine)		 -Laser treatments   -Consultations with pain specialists or psychiatrists -Sunscreen
-Skin care
* IPL = intense pulsed light, † Nd:YAG = neodymium/yttrium–aluminum–garnet laser, ‡ PDL = pulsed dye laser, § PDT = photodynamic therapy, ** CO2 laser = carbon dioxide laser.

2.1. Skin Care and General Recommendations

Dermatologists have an important role in educating patients about the importance of skin care and the avoidance of triggers [9][10]. Protecting and supporting the epidermal barrier function is critical in rosacea patients. Gentle cleansing and the use of moisturizers strengthen the epidermal barrier function, and sunscreens provide UV protection [3][11][12]. Despite the lack of randomized trial data, clinical experience supports a number of common skin care practices [13]. Alcohol, hot beverages, and sun exposure are the main triggers of rosacea and affect the pathogenesis. The avoidance of triggers and irritant cosmetics and the usage of sunscreens, especially to prevent UVB, are recommended for rosacea patients [3][14].

2.2. Treatments for Erythematotelangiectatic Rosacea

2.2.1. Topical Treatment for Erythematotelangiectatic Rosacea

The selective alpha-2 adrenergic agonist 0.5% brimonidine topical gel has significant vasoconstrictive activity. In a Cochrane meta-analysis, 41% of patients treated with topical gel 0.5% brimonidine had a significant reduction in erythema compared to 20% of patients in the placebo control group [15]. After the application of brimonidine to the face, a reduction in erythema is observed within 30 min, with peaks between 3 and 6 h, and then the benefit diminishes. The use of brimonidine may also cause immediate erythema, pruritus, burning, and flushing, as well as rebound erythema [13]. Oxymetazoline hydrochloride 1% cream, an alpha-1 adrenergic agonist and partial alpha-2 adrenergic agonist, approved by the Food and Drug Administration (FDA) for the treatment of persistent erythema, was found to be significantly effective in reducing erythema in two randomized controlled trials [11][15]. Both drugs provide local vasoconstriction but do not reduce telangiectasias or other symptoms of the disease. Brimonidine also has additional mast cell-mediated anti-inflammatory properties and acts as a barrier [16][17]. In addition, a study showed that brimonidine was beneficial against alcohol-induced flushing and provided satisfaction in rosacea patients [18]. Both topical drugs could be used with topical, systemic, or instrumental therapies for rosacea. Although they are not sufficient for reducing persistent erythema, vasoconstrictors are a useful adjunctive therapy option in rosacea [3]. In a single anecdotal study, the topical application of the beta blocker drug timolol displayed a degree of improvement in erythema. However, the improvement was not statistically significant [19]. Topical tranexamic acid, a conventional treatment for melasma, may improve lesions in rosacea by modifying the immune system and angionesis [5]. Two studies of topical trenexamic acid for the treatment of erythema and telangiectasia in rosacea patients showed promising therapeutic effects with a good safety profile [20][21]. In one study, topical 1-methylnicotinamide, a metabolite of nicotinamide (vitamin B3), 0.25% gel was used to treat 34 patients with rosacea, including both erythematotelangiectatic and papulopustular subtypes. Improvement, defined as good or moderate, was seen in 26 patients. One patient reported skin irritation and withdrew from the study [22].

2.2.2. Systemic Treatment for Erythematotelangiectatic Rosacea

Despite the lack of randomized trials, antihypertensive drugs are the only potentially effective therapy options for erythema and flushing [15]. Therapeutic options entail the use of alpha-2 adrenergic agonists, such as clonidine, and beta blockers like propranolol and carvedilol. Clonidine showed promising potential as a modifier of malar temperature and circulation, but a small placebo-controlled study failed to show clinical efficacy, also limited by its side effects [1][13][23]. Rilmenidine, a partial agonist of alpha-1 and alpha-2 adrenergic receptors, has been tried in a single clinical trial, it presented to be active in some cases of erythema, but the result was not significant [24].
Propranolol, a non-selective beta blocker, has been shown to reduce flushing by blocking beta receptors in cutaneous blood vessels. However, it is not recommended for rosacea because of adverse effects such as hypotension and bradycardia. In one case report, carvedilol therapy resulted in significant resolution of facial flushing within 2 weeks without side effects such as hypotension and bradycardia [25]. There are no placebo-controlled trials in the literature demonstrating the efficacy of beta blocker treatment in rosacea, yet it remains the most widely used treatment. Beta blocker therapy requires evaluation by a cardiologist with the performance of an electrocardiogram especially in patients over 50 years of age. Consequently, combination therapies with beta blockers accompanied by laser techniques or topical vasoconstrictive therapies may lead to more long-lasting and significant effect in rosacea [3].

2.2.3. Instrumental Treatment for Erythematotelangiectatic Rosacea

Light therapies and laser treatments, including intense pulsed light (IPL) 500–1200 nm, pulsed dye laser (PDL) 585–595 nm and long-pulsed neodymium:yttrium-aluminum-garnet laser (Nd:YAG) 1064 nm are effective treatment modalities for rosacea [26]. IPL generates a non-coherent light beam within the wavelength range of 500–1200 nm by employing cut-off filters for vascular lesions, specifically at 515, 550, 560, 570, and 590 nm [26]. In a study of 102 patients with mild to severe rosacea, IPL therapy was utilized with a 530 nm filter administered at intervals of one to three weeks and fluences varying from 10–30 J/cm2. For patients with acneiform breakouts in addition to telangiectasias, a 420 nm filter was used with fluences of 10–20 J/cm2. The study found that 80% of patients experienced a reduction in redness, 78% reported an improvement in flushing and skin texture, and 72% experienced a decrease in acneiform breakouts. No complications or adverse effects were identified [27]. In a separate study, thirty-four patients underwent treatment using IPL 515–1200 nm along with a 560 nm cut-off filter. The fluence range utilized was 24–32 J/cm2, and four treatments were administered to the face at 3-week intervals. The study observed reductions of 39% in erythema on the cheeks and 22% on the chin. The photographic improvement in redness and visible blood vessels was 46% and 55%, respectively. These results were maintained for 6 months with only minor side effects [28]. PDL emits light at a wavelength of 585–595 nm, which corresponds with the absorption peak of oxyhemoglobin that targets the superficial vessels [26]. In a study, PDL efficiently decreased telangiectasia in all 11 patients following a solitary treatment, with noteworthy outcomes evident after 6 weeks. Telangiectasia ratings decreased from 2.7 to 2.4 at lower fluences without purpura, while purpuragenic treatments led to a further decrease to 1.4 from the baseline [29]. Also, PDL has demonstrated comparable efficacy in decreasing symptoms and signs of rosacea, as observed in a controlled study comparing it to IPL. PDL (non-purpuragenic fluences: 7 J/cm2, 10 mm spot size, 6-ms pulse duration) and IPL (560 nm filter, pulse train: 2.4 and 6.0 ms, pulse delay: 15 ms, fluence: 25 J/cm2) were able to significantly and equally reduce the symptoms as erythema and telangiectasia when compared to the control group [30]. Although infrequently employed in rosacea treatment, the Nd:YAG laser (1064 nm) seems to be a secure and efficacious method for dealing with ETR [26]. In two split-face studies involving 14 patients, the non-purpuragenic 595 nm PDL exhibited superior efficacy in reducing facial redness in erythematotelangiectatic rosacea patients compared to the Nd:YAG laser. Nevertheless, Nd:YAG was determined to be a reliable and harmless treatment for rosacea. There were no noteworthy adverse effects noted. Additionally, the study has indicated that NdYAG laser is less uncomfortable than PDL and may offer advantages for patients with darker skin [31].
Another treatment modality for rosacea is photodynamic therapy (PDT), which has been shown to improve erythema and telangiectasia in small series when used in conjunction with lasers and light therapies [32]. A total of 30 patients diagnosed with erythematotelangiectatic and papulopustular rosacea were included in a retrospective study. These patients underwent a total of 39 treatments as part of various combinations involving blue light + PDL, blue light + IPL, blue light + PDL + IPL, or blue light + red light + PDL + IPL. Laser and light sources were utilized in a sequential manner with ALA (aminolevulinic acid) 20% serving as the photosensitizer. Treatment consisted of red light (630 nm, 37 J/cm2, 8 min), blue light (417 nm, 10 J/cm2, 15 min), PDL (5–15 J/cm2, 0.5–40 ms), and IPL (560 nm cutoff filter, 15–22 J/cm2, 3.5–4 ms). The improvement of rosacea was mild to moderate, while that of skin quality was moderate to good. The authors observed no noteworthy difference in improvement among patient groups [33]. Even the clear effect of PDT on reducing telengiectasia, results are shown to be transient [3]. On the other hand, it is crucial to select the proper parameters in studies of laser and light-based therapies, as high levels of photodynamic therapy may induce a worsening of rosacea [34].
Nevertheless, based primarily on observational studies, laser treatments are practically effective on erythema and telangiectasia, and no other laser method seems to be superior to another. Although a reduction in flushing in rosacea patients has been observed by clinicians, there is no significant result of reducing the number and duration of flushing by using laser or IPL methods. However, the shrinkage of the vessels by these treatment methods led researchers to assume that they are beneficial for the symptoms of flushing by reducing the number of attacks [3].

2.2.4. Injection Treatment for Erythematotelangiectatic Rosacea

Botulinum toxin appears to be an injectable method for rosacea patients, but studies are small groups and case reports. A double-blind, placebo-controlled, split-face study showed a significant decrease in the erythema index in the group treated with botulinum toxin. In this research, fifteen units of botulinum toxin were intradermally injected into one cheek, while the other cheek received a placebo injection with normal saline. Injections were administered at 1 cm intervals, with a volume of 0.05 mL at every point (30 points) within a 5 cm wide and 6 cm long section of the cheek, following a grid pattern [35]. A case report also demonstrated that intradermal botulinum toxin injections significantly reduced erythema, edema, telangiectasias, and flushing. In this research, botulinum toxin was diluted to a concentration of 10 units/mL and administered intradermally in the hypervascular and telangiectatic centrofacial area as 0.05 mL microdroplet injections, spaced 0.5 cm apart [36].
Erenumab represents a promising therapeutic alternative as it is a human monoclonal antibody that binds to the calcitonin gene-related peptide (CGRP) receptor. An open-label phase II study is underway to assess the effectiveness and tolerability of subcutaneously administering 140 mg of erenumab (AMG 334) every 4 weeks for persistent flushing and redness [37].

2.3. Treatments for Papulopustular Rosacea

2.3.1. Topical Treatment for Papulopustular Rosacea

For the treatment of papules and pustules, recommended therapies include topical azelaic acid and topical ivermectin (high-certainty evidence), and topical metronidazole and topical minocycline (moderate-certainty evidence) [15]. In addition, a systematic review and meta-analysis demonstrated that topical ivermectin is the most effective topical treatment for papulopustular rosacea and provides the greatest psychological benefit to these patients [38]. Topical ivermectin is effective in clearing almost all papules and pustules, especially in moderate to severe rosacea [39].
Two phase 3 randomized clinical trials involving 751 and 771 participants, respectively, evaluated the use of minocycline foam for the treatment of moderate to severe papulopustular rosacea. The trials found the foam to be effective and safe [40]. In addition, topical minocycline 3% gel was shown to significantly reduce inflammatory lesions compared with the placebo in patients with papulopustular rosacea in a prospective, 12-week, double-blind study involving 270 patients [41].
Topical treatment with benzyl benzoate (+crotamiton) normalized Demodex densities in a study of 344 patients, with symptoms disappearing in more than 80%, particularly in patients with good compliance [42]. In a retrospective study of 394 patients, consisting of 117 patients with rosacea and 277 patients with demodicosis, topical treatment with benzyl benzoate (+crotamiton) yielded similar results across all patient cohorts. The treatment proved to be effective in 46% of patients, with a curative rate of 20%. Higher dose regimens exhibited greater effectiveness compared to lower dose ones [43].
A study involving six women diagnosed with papulopustular rosacea or rosacea with irritant contact dermatitis found that soaking in a solution of tranexamic acid significantly reduced erythema, as well as decreased itching, flushing, and burning, without any reported side effects [44].

2.3.2. Systemic Treatment for Papulopustular Rosacea

Systemic oral treatments are recommended in the management of moderate to severe papulopustular rosacea [45]. Doxycycline modified-release treatment at 40 mg, as well as isotretinoin and minocycline, which have demonstrated moderate-certainty evidence, should be considered as potential interventions for reducing papules and pustules, according to the updated systematic review on treatments for rosacea [15]. Doxycycline is an effective drug in the tetracycline antibacterial group for papulopustular rosacea. It can be given as a low dose of 40 mg daily for prolonged periods. In severe cases, doxycycline could be used at 200 mg/day for 4 weeks with a tapering regimen [46][47]. Isotretinoin at a low dose of 0.3 mg/kg reduces inflammation in rosacea subtype 2 [48].
Metronidazole, azithromycin, and clarithromycin are other systemic antibiotic options. In addition, ivermectin may be considered as an antiparasitic therapy for papulopustular rosacea [45]. Studies on the efficacy of zinc sulfate treatment for rosacea have yielded conflicting results. One study conducted on 25 patients indicated that taking 100 mg of zinc sulfate three times a day is a highly effective treatment, as it led to significant improvements in rosacea severity scores [49]. However, a randomized double-blind study found no significant difference in rosacea improvement between those who were administered oral zinc sulfate at a dosage of 220 mg twice a day and those who were given a placebo [50].
Hydroxychloroquine (HCQ) displays potential as a viable treatment alternative for patients affected by rosacea [5]. In a study, the results indicated that HCQ can partially reduce the mast cell-associated inflammatory response in a rosacea-like mouse model, suggesting its potential as a therapeutic mechanism for rosacea. Furthermore, patients who underwent HCQ treatment for a duration of eight weeks experienced a decrease in erythema and inflammation, resulting in positive outcomes [51]. In an 8-week period, a randomized, double-blind, double-dummy study was conducted with 66 patients. The total score changes in the Rosacea-Specific Quality of Life instrument in the HCQ group were found to be noninferior in comparison to the doxycycline group. In addition, the HCQ group reported excellent improvement rates in the Clinician’s Erythema Assessment scores of ‘clear’ or ‘almost clear’, which were nearly equal to those in the doxycycline group [52].
Eliminating small intestine bacterial overgrowth (SIBO) using rifaximin resulted in an almost complete or complete control of papulopustular rosacea, and these outcomes remained consistent for a minimum of 9 months. Objective assessments suggest a substantial improvement [53]. In a separate study, patients with rosacea and SIBO who underwent successful eradication therapy were able to remain symptom-free from rosacea for up to three years during the follow-up [54]. In a clinical trial, individuals with rosacea and H. pylori infection were administered H. pylori eradication therapy. Subsequently, the grading score for rosacea decreased dramatically, indicating that the elimination of H. pylori in individuals with rosacea can alleviate symptoms [55]. One review suggested that all patients with rosacea should be tested for H. pylori and treated if positive, as this may lead to improved outcomes [56].

2.3.3. Instrumental Treatment for Papulopustular Rosacea

IPL treatment, using a 420 nm filter and fluences ranging from 10 to 20 J/cm2, effectively reduced acneiform breakouts by 72% [27]. An Nd: YAG (1064 nm) laser has proven to be effective in treating papulopustular lesions of rosacea in an open clinical trial, especially in cases where traditional therapy has failed [45]. PDT, such as in the case of erythematotelangiectatic rosacea, has demonstrated a decrease in symptoms for papulopustular rosacea [33].

2.3.4. Injection Treatment for Papulopustular Rosacea

Injection therapy using IL-17 inhibitors has recently been utilized in subcutaneous injections for the treatment of rosacea. In a preliminary non-blinded study initiated by the investigator in which 20 patients were given secukinumab (300 mg per week for 5 weeks and then once a month for 2 months), noteworthy decreases in both the papules and the global severity score were observed. However, at least one infection was experienced by 39% of the patients in this research who received a minimum of one dose [57].

2.4. Treatments for Phymatous Rosacea

Before selecting the phyma treatment, it is necessary to evaluate whether the rosacea is inflamed or noninflamed, according to the latest update for rosacea treatment issued by the global Rosacea Consensus (ROSCO) panel. For inflamed phyma, it is recommended to undergo treatment with topical retinoids, oral doxycycline, and oral isotretinoin. On the other hand, for noninflamed phyma or fibrotic phyma, the recommended methods are instrumental or surgical therapies [10]. A recent report in the literature showcased the efficacy of CO2 laser ablation in treating rhinophyma in a patient, yielding positive results. In a recent retrospective study involving 28 patients, it was recommended that after-shave excision of rhinophyma be complemented with the use of a porcine extracellular matrix. This treatment was found to decrease the number of dressing changes needed and reduce the time to achieve re-epithelialization [58].
When medical treatments prove to be unsatisfactory, a range of surgical techniques can be helpful in treating phymatous rosacea. Scalpel or razor blade excision, in the form of a partial excision (superficial decortication) of hypertrophic tissue to allow for the re-epithelialization of pilosebaceous tissue, is a fast and effective cosmetic procedure with satisfactory results. Additionally, dermabrasion is primarily employed as a supplementary treatment to other modalities. Also, electrosurgery and electrocautery are surgical techniques, in which an electrosurgical current is applied, that could be used for phymatous rosacea [59].

2.5. Treatments for Ocular Rosacea

Recommendations for the treatment of ocular rosacea include a combination of eyelid hygiene and the systemic administration of tetracycline drugs, as suggested in an interdisciplinary review [60]. Therapeutic options comprise oral omega-3 fatty acids with moderate-certainty evidence, cyclosporin ophthalmic emulsion, and doxycycline with low-certainty evidence [15]. Pediatric patients with ocular rosacea received treatment consisting of warm compresses, eyelid scrubbing, preservative-free artificial tears, topical antibiotics, topical steroids, topical cyclosporine, oral doxycycline, azithromycin, and erythromycin suspension in a published study [61]. During a clinical observation, the utilization of intense pulsed light (IPL) with proper eye shield usage to protect the eyes aided in the reduction in dry eye symptoms for patients with rosacea after undergoing treatment for periocular facial skin [62]. An enhanced water-soluble silver (I) compound of metronidazole was found to relieve ocular rosacea symptoms in three patients experiencing severe cases [63]. Surgery, such as blepharoplasty, may be required in severe cases [45].

2.6. Treatments for Granulomatous Rosacea

Granulomatous rosacea has a chronic and challenging course to treat. It is difficult to manage with currently available therapeutic agents, making it a continuing challenge for dermatologists. Treatment modalities are presented in case reports and case series within the literature [5]. Topical treatments like pimecrolimus cream, azelaic acid gel, and topical ivermectin have been proven to be effective. Systemic oral therapies like minocycline, dapsone, doxycycline, metronidazole, steroids, and isotretinoin have also shown efficacy in treating granulomatous rosacea. The treatment for papulopustular rosacea can be used for granulomatous rosacea in practice. Moreover, chromophore gel-assisted phototherapy and intense pulsed light (IPL) treatments have been successful [5][45].

2.7. Treatments for Rosacea Fulminans

A comprehensive review indicates that rosacea fulminans would benefit from systemic corticosteroids and/or isotretinoin treatment to enhance symptoms and reduce scarring [4]. During systemic oral steroid treatment, to prevent relapses following steroid treatment cessation, it is recommended to undergo a regimen of oral prednisone at a dose of 40–60 mg/day, accompanied by a low-dose of isotretinoin 2 weeks later. The steroid taper should be slow while continuing isotretinoin until a cumulative dosage of 150 mg/kg is reached. Isotretinoin dosages ranged between 0.2 and 1.0 mg/kg/day, with 0.5 mg/kg/day being the most commonly used dosage [4].

2.8. Treatments for Neurogenic Rosacea

Clinical trials have not shown any therapeutic approaches to be effective in the treatment of neurogenic rosacea. Depending on specific symptoms, individualized treatment options may be necessary, such as beta blockers, neuropathic pain medication, laser treatments, or medical treatments for rosacea [3]. There are also unconventional treatments available for neuropathic pain, including gabapentin, pregabalin, and pain-modifying antidepressants such as duloxetine for neurogenic rosacea [7][8]. Psychiatric care or psychotherapy may be beneficial in certain cases. Dermatologists should refer patients who are unresponsive to conventional treatments to pain specialists or psychiatrists [3].

This entry is adapted from the peer-reviewed paper 10.3390/dermato3040019

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