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1. What items in the specific history would help you distinguish rosacea from lupus erythematosus (LE)?

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37 Rosacea (Acne Rosacea)

CLINICAL APPLICATION QUESTIONS

A 50-year-old woman is seen in your office for facial discoloration that has been very persistent for the past 2 months. She also complains of frequent styes and constant gritty eye discomfort with lid granulation each morning. Initial observation shows a striking but- terfly erythema.

1. What items in the specific history would help you distinguish rosacea from lupus erythematosus (LE)?

2. What physical findings would help you to distinguish rosacea from LE?

3. What laboratory data are indicated?

4. Assuming that physical findings and lab results are consistent with rosacea, what is the most appropriate treatment for this patient?

APPLICATION GUIDELINES Specific History

Onset

Rosacea is a disorder that presents most typically in the third, fourth, and fifth decades of life. It is seen occasionally in younger adults, and there are uncommon reports of oth- erwise typical rosacea in childhood. Presentation in adult patients beyond the fifth decade is fairly common. Women seem more frequently affected than men. This preference may be misleading, however, because of male machismo that prevents seeking help for skin disorders. Men are subject to the more severe and deforming variants. Although heritage is not an absolute protection, rosacea is rare in heavily pigmented skin types, whereas western Europeans, especially those of Celtic ancestry, are especially vulnerable. Onset may be explosive and may follow exposure to one of the provoking factors listed below.

Most cases start insidiously, but inexorably worsen without medical intervention. Many patients will state on the initial visit, “I have watched this change for months (or years) and I finally have to do something about it.” The earliest and most persistent symptoms are erythema and fine telangectasias distributed symmetrically over the central face, but sparing the eyelids, upper forehead, and lips.

Evolution of Disease Process

The erythema and telangectasia of rosacea initially wax and wane from day to day, but gradually become more conspicuous and more persistent. The disease may retain this morphology throughout the course of the patient’s life. This is referred to as erythematous

359

From: Current Clinical Practice: Dermatology Skills for Primary Care: An Illustrated Guide D.J. Trozak, D.J. Tennenhouse, and J.J. Russell © Humana Press, Totowa, NJ

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telangiectatic rosacea. In a significant number of cases, the course is punctuated by attacks of dusky rose-red papules that occur within the areas of erythematous skin. About 20% of cases will show pustules replacing some of the papules. The pustules are usually not tender and, except in rare instances of concurrent acne vulgaris, comedones are absent.

These acute exacerbations are often associated with acute edema that is visible and pal- pable. This stage is referred to as papulopustular rosacea.

A small number of cases progress to large nodular lesions with permanently thickened skin, coarse pores, sebaceous gland hyperplasia, and persistent facial edema. This uncom- mon but deforming variant almost exclusively affects men and is called glandular hyper- plastic rosacea.

During acute exacerbations, many patients complain of an uncomfortable suffused feeling of the facial skin and, in the case of nodular lesions, overt tenderness. Many also remark after treatment that because of the insidious onset, they failed to appreciate how uncomfortable the skin areas had become.

Without therapy, most patients have persisting symptoms punctuated by acute exacer- bations often triggered by identifiable environmental factors discussed below. With med- ication, almost all rosacea patients can be controlled, and a substantial number go into complete remission. In one study, after adequate systemic treatment with oral tetracycline, 31% of patients remained free of disease during a 4-year follow-up. The other 69%

relapsed, most within the first 6 months. Some patients with early rosacea remained asymptomatic without treatment for several years after complete control was achieved with systemic medication.

Special forms of rosacea include the following:

Disseminated rosacea: In rare cases, other locations such as the hairless scalp, V of the chest, upper mid-back, and wrists may be involved with otherwise typical lesions.

However, the central face is the most constant and characteristic site.

Lupoid/granulomatous rosacea: Widespread red-brown papules and nodules appear on a background of dusky erythema. With diascopy using a glass slide, the lesions show the apple-jelly nodule change seen also with lesions of lupus vulgaris. Areas that are usu- ally spared in common rosacea (such as the eyelids and perioral skin) are affected in lupoid rosacea. Biopsy shows granulomatous histology.

Complications of rosacea may include:

Ocular rosacea: Eye symptoms occurred in more than 50% of cases in one study.

Practical experience suggests that the actual incidence is about 10% or less. In most cases, findings are those of a low-grade conjunctivitis manifest by tenderness, a gritty discom- fort, lid granulations, and conjunctival injection. Other eye complications reported include meibomianitis, trichiasis, episcleritis, chalazion, and hordeolum. Rosacea-associated ker- atitis can cause corneal scarring and blindness. Any rosacea patient with pain, photopho- bia, or altered visual acuity should have an ophthalmologic evaluation and prompt systemic treatment for the rosacea. The ocular complications respond to systemic rosacea medication provided corneal scarring has not yet occurred.

Rhinophyma: A progressive alteration of the nose develops in some male rosacea

patients. Contrary to popular belief, this is not a sign of alcoholism. Deformity and coarse-

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ness of the nasal skin with enlarged patulous follicles begins on the distal nose and grad- ually spreads. The hypertrophy may be asymmetric, causing marked distortion. On rare occasions, the tip of the chin and the earlobes may be similarly affected. Treatment with standard systemic medication for rosacea will improve the color and control inflammatory lesions, but has no effect on the thickening or deformity. A dermatologic referral is appro- priate. Surgical revision can dramatically improve the changes.

Rosacea lymphedema: A persistent nonpitting edema of the forehead, cheeks, chin, or (on rare occasions) the earlobes develops during the course of chronic rosacea. Color varies from mild to intense erythema. Standard medications have little effect on this com- plication.

Evolution of Skin Lesions

The intensity of the erythema, telangectasia, and edema varies from day to day.

However, over long time periods, they become progressively more persistent and wide- spread. The papular and nodular lesions are often quite chronic, and advanced lesions may require several weeks to resolve even with systemic treatment. A certain number of the papular lesions in some cases develop a dome-shaped pustule at their apex. Some pustules are quite small and can be best discerned with the aid of a hand lens. As the pustules dete- riorate, they form a small hemorrhagic crust. The papular and nodular lesions of rosacea, in contrast to those of acne vulgaris, do not scar.

Provoking Factors

Patients who develop rosacea are almost universally flushers and blushers.

Environmental factors that stimulate this vasomotor instability will aggravate the disease and may precipitate the initial attack and subsequent acute exacerbations. Chronic sun- induced degenerative changes in the connective tissue that supports the dermal blood vessels also appears to play a permissive role in the onset of the disease. Common envi- ronmental triggers include the following:

1. Acute sunburn with its attendant erythema.

2. Ingestion of piping-hot liquids, irrespective of their content.

3. Persistent diet of hot or spicy foods.

4. Regular use of alcoholic beverages.

5. Medications that produce vasodilation have become increasingly important in this regard over the last quarter-century. β-blocking agents, acetazolamide, nitrates, and psoralens have all been reported to exacerbate the disease. Any medication that pro- duces prolonged vasodilation should be considered suspect, especially if there is a temporal relationship between its introduction and increased rosacea activity.

Self-Medication

In contrast to acne, self-treatment is not a significant problem with rosacea patients.

Supplemental Review From General History

A review of prescription and proprietary medications, dietary habits, and alcoholic

beverage use is indicated. Questions regarding any ocular symptoms or visual changes are

also important. Otherwise, rosacea does not have any systemic manifestations.

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Dermatologic Physical Exam Primary Lesions

1. Patches of pink to dusky-red erythema covered with a network of fine dilated (telangiectatic) blood vessels (see Photo 37).

2. Dusky-red inflammatory papules (see Photo 38).

3. Dusky-red inflammatory nodules (see Photo 39).

4. Dome-shaped pustules (see Photo 40).

Secondary Lesions

1. Acute palpable edema of the facial skin that is present during attacks and resolves during periods of control (see Photo 41).

2. Chronic persistent edema of the involved skin that is unresponsive to treatment.

3. Chronic noninflammatory papules and nodules seen in glandular hyperplastic rosacea.

Although they are usually primary lesions, here papules and nodules may occur as secondary lesions.

Distribution

Microdistribution: None.

Macrodistribution: Central forehead, nose, chin, and butterfly-flush area of the face (see Fig. 5). The upper forehead, lips, and eyelids are spared except in the lupoid variant and in cases of topical steroid-induced rosacea. Other locations may be involved in the uncommon disseminated variant.

Configuration

Grouped papules, nodules and/or pustules on a background of telangiectatic erythema.

Indicated Supporting Diagnostic Data

In most instances, rosacea is a clinical diagnosis. On rare occasions, biopsy may be indicated when individual lesions simulate other conditions or when there is a question of rosacea versus cutaneous lupus erythematosus. In these instances, a dermatologic consul- tation is indicated. The skills of the dermatologist in physical examination may avoid needless expense and manipulation of the patient.

Therapy

Rosacea is a disease that, if left untreated, can progress through a continuum of change to a point where irreversible damage occurs. This potential, plus the emotional and actual physical discomfort, make rosacea treatment more than just cosmetic.

Prevention

Avoiding sunburn, extreme environmental heat, prolonged hot baths, ingestion of piping-hot liquids, hot spicy meals, and alcoholic beverages will minimize the attacks. Once good control of the disease is achieved, occasional dietary relaxation can usually be allowed.

If a medication such as a β-blocking agent is implicated, the medication should be changed.

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Systemic Therapy

Oral tetracycline has been recognized as a safe and effective treatment for rosacea for more than 30 years. The mechanism of action in this disease is not known. Most cases respond to an initial dose of 250 mg BID and can be maintained on a single capsule daily.

The disease shows no tendency to become resistant to this medication and, if increased activity is noted in a patient, other external provoking factors should be sought.

Tetracyclines are often combined initially with a nonfluorinated group VI or group VII steroid cream or lotion (see Chapter 4, Table 1). Desonide 0.05% and 2.5% hydrocorti- sone are common examples. Fluorinated corticosteroids, however, are contraindicated.

Topical steroids alone are not effective monotherapy. In severe or disseminated rosacea, higher doses of 250 mg tetracycline QID or use of doxycycline or minocycline may be indicated. Minocycline is also helpful in patients with GI intolerance to tetracycline and in female patients who are prone to vaginal candidiasis. Systemic tetracyclines control the ocular complications of rosacea provided irreversible injury has not occurred. Systemic metronidazole is also effective, but has never been used on a chronic basis because of con- cerns regarding side effects. Severe or recalcitrant rosacea will respond to isotretinoin.

These cases should be referred to a dermatologic consultant.

Figure 5: Macrodistribution of rosacea.

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Topical Therapy

Topical metronidazole is available as a 0.75 to 1% cream, 0.75% gel, or lotion for the treatment of rosacea. All are effective as monotherapy in mild to moderate erythematous telangiectatic rosacea, and can be used in more advanced cases with systemic tetracycline to induce remissions and then maintain control while the systemic medication is with- drawn. Equally effective are premade prescription products containing sodium sulfac- etamide. They are available in clear and tinted formulations. Patients with chronic renal disease, or sulfonamide or sulfite sensitivity, should not use these products. Azaleic acid gel 15% has also been approved for treatment of mild to moderate rosacea. In a head-to- head study it was superior to 0.75% metronidazole gel.

Conditions That May Simulate Rosacea Acne Vulgaris

The two diseases may occur concurrently. Otherwise, their clinical features distin- guish them. Acne does not have the background of erythema and dilated blood vessels.

Comedones and inflammatory cysts are present with acne (features not seen in rosacea).

Acne frequently involves the central chest and back, and often leaves scars.

Perioral Dermatitis

This localized eruption presents with pinpoint papules and pustules in the perioral and perinasal areas, and is seen almost exclusively in females. The lesions are so small that a hand lens is often required to appreciate their morphology. The background skin is eczematous.

Discoid and Systemic LE

Both discoid and systemic lupus erythematosus can be confused with the erythema- tous telangiectatic variant of rosacea. Papules and pustules do not occur, so there should be no confusion with the other forms of rosacea. Neither form of LE waxes and wanes dra- matically from day to day as does rosacea. Lesions of both forms of lupus tend to extend beyond the usual distribution of rosacea and, with discoid lupus, the scaling, atrophy, scar- ring, and pigmentary changes help to distinguish it. Biopsy may help in difficult cases;

however, direct immunofluorescence gives false-positive results and should not be used.

Steroid Rosacea

Although topical steroids have been used as adjunctive treatment in rosacea for years,

fluorinated topical steroids can aggravate active rosacea and can produce a rosacea-like

eruption in persons without a previous problem. The drug-induced form initially shows

erythema and telangectasia, but can progress to a papulopustular phase. Involvement of

the entire forehead, lips, and eyelids (areas normally spared in spontaneous rosacea) is an

important clue.

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ANSWERS TO CLINICAL APPLICATION QUESTIONS History Review

A 50-year-old woman is seen in your office for facial discoloration that has been pro- gressive for the past 6 months. She also complains of frequent styes and constant gritty eye discomfort with lid granulation each morning. Initial observation shows a striking but- terfly erythema.

1. What items in the specific history would help you distinguish rosacea from LE?

Answer:

a. Gradual onset and progression.

b. A history of remissions and exacerbations.

c. Ocular symptoms.

d. A history of blushing and flushing (vasomotor instability).

e. Exacerbations when exposed to known provoking factors.

2. What physical findings would help you to distinguish rosacea from LE?

Answer:

a. Dusky-red inflammatory papules and nodules.

b. Dome-shaped pustules.

c. An active conjunctivitis.

3. What laboratory data are indicated?

Answer: An antinuclear antibody (ANA) test would be appropriate because of the similarity between the two eruptions. Extensive serologic testing for LE is indi- cated only if other findings raise a significant suspicion that this is not rosacea.

4. Assuming that physical findings and lab results are consistent with rosacea, what is the most appropriate treatment for this patient?

Answer: Systemic therapy with tetracycline or a tetracycline-derivative antibi-

otic. This will control her ocular and cutaneous symptoms.

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