• Chronic acne-like eruption on the face of middle-aged and older adults, associated with facial flushing
• Primary involvement occurs over the flushed areas of the cheeks and nose
• More common in women but more severe in men
Rosacea is a common, chronic, progressive inflammatory skin disorder in which the nose and cheeks are abnormally red and may be covered with pimples similar to those seen in acne (see that chapter). Rosacea was originally called “acne rosacea” because its inflammatory papules and pustules so closely mimic those of acne. However, acne is based on the interaction of abnormal keratinization, increased sebum production, and bacterially induced inflammation, whereas the inflammation in rosacea is vascular in nature. Rosacea generally occurs in patients between the ages of 25 and 70 years, and it is much more common in people with fair complexions. Women are three times more likely than men to have rosacea, although the disease is generally more severe in men. At least 13 million Americans are known to be affected.1
Rosacea is divided into the following three stages, but since progression does not necessarily occur, rosacea is also often divided into four specific subtypes (erythematotelangiectatic, papulopustular, phymatous, and ocular): 1,2
• Stage I: In stage I, or erythematotelangiectatic rosacea, redness and flushing of the skin are triggered by hot beverages, spicy foods, and alcohol and may persist for hours; spider veins (telangiectasias) are noticeable on the central third of the face; and burning, stinging, and itching after the application of cosmetics, fragrances, and sunscreens become a major complaint.
• Stage II: Inflammatory whiteheads and pimples are the hallmarks of stage II, or papulopustular rosacea. Flushing, telangiectasia, increased skin oiliness (seborrhea), and minimal facial pore enlargement become obvious.
• Stage III: A small number of patients progress to stage III, or phymatous rosacea, which is characterized by deep inflammatory nodules, large spider veins, markedly dilated facial pores, sebaceous gland enlargement, and enlargement of the nose (rhinophyma).
Ocular rosacea is the spectrum of eye findings associated with the skin involvement. Ocular rosacea can cause the eyes to have a watery or bloodshot appearance, the sensation of a foreign body, burning or stinging, dryness, itching, light sensitivity, and a host of other signs and symptoms. Sties are a common sign of rosacea-related ocular disease, and some individuals may have decreased visual acuity owing to corneal complications.
It is important to point out that what differentiates the flushing that rosacea patients experience from the flushing that accompanies embarrassment, exercise, or hot environments is the prolonged nature and intensity of rosacea flushing. While normal flushing episodes last from several seconds to a few minutes, the flushing that the typical rosacea patient describes lasts longer than 10 minutes and is more red than pink, with an accompanying burning or stinging sensation. The stimuli that bring on such flushing in rosacea patients may be acutely felt emotional stress, hot drinks, alcohol, spicy foods, exercise, cold or hot weather, and hot baths or showers. However, many times the episodes are without known stimuli.
Causes
The cause of rosacea is poorly understood, although numerous theories have been offered. Included in the factors that have been suspected of causing acne rosacea are the following:
• The mite Demodex folliculorum
• Helicobacter pylori
• Alcoholism
• Lack of stomach acid
• Menopausal flushing
• Local infection
• Food allergies
• B vitamin deficiencies
• Gastrointestinal disorders
Most cases of rosacea are associated with moderate to severe seborrhea (oiliness), although sebum production is not increased in many. Vasomotor lability is prevalent, and migraine headaches are three times more common in persons with rosacea than in age-and sex-matched controls.
There is also emerging evidence for a role for Helicobacter pylori in rosacea. It is known that H. pylori infection increases the production of several vasoactive substances such as histamines, prostaglandins, and leukotrienes. However, these vascular mediators are found only with H. pylori strains that also produce a specific cytotoxin, CagA. The presence of H. pylori capable of producing this cytotoxin may be more important in rosacea than that of other strains. When the presence of CagA was assessed in 60 rosacea patients and compared with control subjects indigestion researchers found that when infected with H pylori, 67% of rosacea patients, vs. only 32% of controls, had positive findings for CagA. After eradication of H. pylori infection in the rosacea patients, symptoms disappeared in almost all patients (51 of 53).3
The bottom line is that since many of the implicated triggers of rosacea are experienced by healthy people who never go on to develop the symptoms or signs of rosacea, rosacea-prone individuals very likely have an inherent sensitivity to these triggers.
Therapeutic Considerations
One of the first recommendations is to avoid those stimuli that tend to exacerbate the disease—exposure to extremes of heat and cold, excessive sunlight, and ingestion of hot liquids, alcohol, and spicy foods. The conventional medical treatment of rosacea is usually oral tetracycline, especially for the papular or pustular lesions, although this treatment usually only controls rather than eradicates the disease. Topical therapy for rosacea using antibiotics or synthetic retinoids is generally less successful than systemic antibiotic treatment. Also, although topical corticosteroids may initially improve signs and symptoms, long-term corticosteroid therapy is not advisable because it may actually lead to rosacea. The treatment of chronic skin changes and severe rhinophyma may require laser treatments and surgical intervention, respectively.
The natural approach to rosacea is to try to identify and eliminate contributing factors if possible. Key factors to address are hypochlorhydria (lack of stomach acid), eradication of Helicobacter pylori,elimination of food allergies, and optimal intake of B vitamins.
Hypochlorhydria
Gastric analysis of patients with rosacea has led to the belief that it is the result of hypochlorhydria.4 Psychological factors, such as worry, depression, and stress, often reduce gastric acidity. Hydrochloric acid supplementation results in marked improvement in those patients with rosacea who have achlorhydria or hypochlorhydria.4,5 Patients with rosacea have also been shown to have diminished secretion of lipase (a fat-digesting enzyme secreted by the pancreas) and to benefit from pancreatic supplementation.6 For more information, see the chapter “Digestion and Elimination.”
Helicobacter pylori
Given the high incidence of hypochlorhydria, it is perhaps not surprising that a high incidence of H. pylori infection in the stomach has also been found in patients with rosacea.7,8 In a pilot study, H. pyloriwas found in 46 of 94 patients with rosacea, 38 of 88 patients with other inflammatory diseases, and 5 of 14 patients without an inflammatory disease. The researchers believed that the flushing reaction in rosacea is caused by gastrin or vasoactive intestinal peptides. They also quoted an Irish study that found that 19 of 20 patients with acne rosacea tested positive for H. pylori.
Another study that evaluated biopsies of sections of the stomach lining found that 84% of 31 patients were H. pylori positive.9 Interestingly, 20% of the patients who tested positive on biopsy tested negative by blood test for the organism. The antibiotic metronidazole is effective in rosacea, and the elimination of H. pylori is also associated with clinical improvement. These factors further incriminate H. pylori. It is interesting to note that patients with rosacea complain significantly more frequently of “indigestion” and use more antacids than the general population.10
Nutritional Supplements
B Vitamins
The administration of large doses of B vitamins has been shown to be quite effective,11 with riboflavin appearing to be the key factor. It is interesting to note that researchers were able to infect the skin of riboflavin-deficient rats with the mite D. folliculorum, but not the skin of normal rats.12 This mite was once considered a causative factor in rosacea and may still be a factor in some patients, especially those with more granulomatous lesions. Evidence suggests that a delayed hypersensitivity reaction in follicles is triggered by D. folliculorum antigens and stimulates the progression of the affection to the papulopustular stage.13
Although B vitamins are important for patients with rosacea, care must be exercised because some patients’ rosacea may be aggravated by large dosages of these common nutrients. There is a case report of a 53-year-old female who presented to a dermatology clinic with a nine-month history of a facial eruption resembling acne rosacea. Treatment with oral hydroxychloroquine, ibuprofen, terfenadine, prednisone, erythromycin, and tetracycline had been tried during the nine months without success. Topical corticosteroids (desoximetasone, hydrocortisone) and cosmetic elimination also yielded no benefit. Patch test showed a positive reaction to nickel. The eruption began at the time of a personal stress when the patient went through a marital separation. To help with her stress, the patient began taking 100 mg per day of pyridoxine and 100 mcg per day of vitamin B12. Discontinuation of the vitamins resulted in dramatic improvement, and with rechallenge, the condition reappeared. The investigators noted that inflammation and exacerbations of acne related to vitamins B2, B6, and B12 have been reported in the European literature.14
Zinc
Zinc supplementation has been shown to be helpful in acne vulgaris and may also be effective in acne rosacea. To test this hypothesis, 25 patients with rosacea were assessed with a clinical score, then randomly allocated to receive either zinc (23 mg from zinc sulfate) or identical placebo capsules three times per day. Following three months of treatment, the patients crossed over. Nineteen patients completed the study. In the group started on zinc, the score before therapy ranged from 5 to 11. The mean started to decrease directly after the first month of therapy with zinc sulfate to a significantly lower level. After the subjects shifted to the placebo treatment, the mean started to rise gradually in the fifth month but remained significantly lower than the levels before therapy. In the group started on the placebo, the score before therapy ranged from 5 to 9. The mean remained high in the first three months of therapy while the patients were on the placebo. After they shifted to zinc sulfate, the mean started to decrease after the fourth month to significantly low levels. No important side effects were reported apart from mild gastric upset in three (12%) of the patients on zinc sulfate. The authors concluded that zinc is a good option in the treatment of rosacea, as it was safe, effective, and without significant side effects.15
QUICK REVIEW
• Rosacea was originally called acne rosacea because its inflammatory papules and pustules so closely mimic those of acne.
• Most cases of rosacea are associated with moderate to severe seborrhea (oiliness).
• One of the first recommendations is to avoid those stimuli that tend to exacerbate the disease—exposure to extremes of heat and cold, excessive sunlight, and ingestion of hot liquids, alcohol, and spicy foods.
• Hydrochloric acid supplementation results in marked improvement in those patients with rosacea who have achlorhydria or hypochlorhydria.
• A high incidence of H. pylori infection in the stomach has also been found in patients with rosacea.
• Although B vitamins are important for patients with rosacea, care must be exercised because some patients’ rosacea may be aggravated by large dosages of these common nutrients.
• Zinc supplementation has been shown to be helpful in acne vulgaris and may also be effective in rosacea.
• Topical applications of azelaic acid (AzA) appear to be extremely effective in papulopustular rosacea.
Topical Treatments
Topical applications of azelaic acid (AzA) appear to be extremely effective in papulopustular rosacea. Initially AzA was released in a 20% cream formulation and was shown in this vehicle to be effective in the treatment of mild to moderate rosacea. A 15% gel formulation of AzA vastly improved the delivery of AzA and has been proved in head-to-head studies to be superior to the 20% AzA cream and as effective as metronidazole cream or gel.16–18 In a meta-analysis of five double-blind trials involving topical AzA (cream or gel) for the treatment of rosacea compared with a placebo or other topical treatments, four of the five studies demonstrated significant decreases in the average number of inflammatory lesions and redness after treatment with azelaic acid compared with the placebo and effects equal to those of metronidazole in papulopustular rosacea. However, no significant decrease in telangiectasia severity occurred with any treatment group.16
TREATMENT SUMMARY
Eradication of H. pylori infection (when present) and control of hypochlorhydria and food intolerance form the basis of therapy. This approach is supported with B-complex supplementation and the avoidance of vasodilating foods.
General Recommendations
See the chapter “Acne” for general recommendations for acne.
Diet
Avoid coffee, alcohol, hot beverages, spicy foods, and any other food or drink that causes a flush. Eliminate from the diet all refined and/or concentrated sugars; foods containing trans-fatty acids such as milk, milk products, margarine, shortening, and other synthetically hydrogenated vegetable oils; and fried foods.
Nutritional Supplements
• A high-potency multiple vitamin and mineral formula as described in the chapter “Supplementary Measures” (but note that the B vitamins may aggravate rosacea in some cases)
• Key individual nutrients:
Zinc: 45 to 60 mg per day for three months, followed by 20 to 30 mg per day thereafter
• Fish oils: 3,000 mg EPA + DHA per day
• One of the following:
Grape seed extract (>95% procyanidolic oligomers): 100 to 300 mg per day
Pine bark extract (>95% procyanidolic oligomers): 100 to 300 mg per day
Some other flavonoid-rich extract with a similar flavonoid content, super greens formula, or another plant-based antioxidant that can provide an oxygen radical absorption capacity (ORAC) of 3,000 to 6,000 units or more per day
• Probiotic (Lactobacillus species and Bifidobacterium species): a minimum of 5 billion to 10 billion colony-forming units per day
• Pancreatin (8 to 10X USP): 350 to 500 mg before meals
• Hydrochloric acid: follow guide on page 136
Topical Treatments
• Topical application of 15% azelaic acid gel