Rosacea (Clinical)

Overview

Epidemiology^[6,8,9]

• Worldwide incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: > 5%
• Age of presentation: 30–50 years old
  • Less common but possible in adolescents and children
• Women > men
• More common in fair-skinned people

Etiology^[6,8‒10]

The exact etiology is not understood, but the following may be associated with rosacea Rosacea Rosacea is a chronic inflammatory disease of the skin that is associated with capillary hyperreactivity. This condition is predominantly seen in middle-aged women, and is more common in fair-skinned patients. Rosacea:

• Genetic predisposition
• Infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
  • Demodex mites Mites Any arthropod of the subclass acari except the ticks. They are minute animals related to the spiders, usually having transparent or semitransparent bodies. They may be parasitic on humans and domestic animals, producing various irritations of the skin (mite infestations). Many mite species are important to human and veterinary medicine as both parasite and vector. Mites also infest plants. Scabies
  • Helicobacter pylori Helicobacter pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter
• Ultraviolet radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma
• Vascular hyperactivity Hyperactivity Attention Deficit Hyperactivity Disorder causing prolonged flushing:
  • Exercise 
  • Hot weather
  • Spicy food
  • Alcohol use
  • Stress

Pathophysiology^[2,6,8,9]

The precise mechanism is unknown. There are 2 proposed theories involving neurovascular and inflammatory responses:

• Environmental exposure → vasoactive peptides are upregulated → capillary hyperreactivity Capillary Hyperreactivity Rosacea → erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion and flushing
• Microbial exposure → immune system Immune system The body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs activation and inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation

Clinical Presentation and Diagnosis

Clinical presentation

Rosacea Rosacea Rosacea is a chronic inflammatory disease of the skin that is associated with capillary hyperreactivity. This condition is predominantly seen in middle-aged women, and is more common in fair-skinned patients. Rosacea may present as 1 of several different clinical phenotypes. These phenotypes are not mutually exclusive, and patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may have features of multiple types with varying symptoms over time.^[1,2,5,6,11]

• Cutaneous manifestations:
  • Centrofacial erythema Centrofacial Erythema Rosacea
  • Phymas (thickened skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions with irregular contours)
    • Nose Nose The nose is the human body’s primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Nose Anatomy (External & Internal) → rhinophyma Rhinophyma A manifestation of severe rosacea resulting in significant enlargement of the nose and occurring primarily in men. It is caused by hypertrophy of the sebaceous glands and surrounding connective tissue. The nose is reddened and marked with telangiectasia. Rosacea (most common)
    • Cheeks Cheeks The part of the face that is below the eye and to the side of the nose and mouth. Melasma (especially medially)
    • Forehead Forehead The part of the face above the eyes. Melasma→ glabellophyma Glabellophyma Rosacea
    • Chin Chin The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. Melasma → gnathophyma Gnathophyma Rosacea
  • Papules and pustules
  • Telangiectasias Telangiectasias Ataxia-telangiectasia
  • Flushing
• Ocular manifestations (seen in > 50% of cases):
  • Conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis
  • Blepharitis Blepharitis Blepharitis is an ocular condition characterized by eyelid inflammation. Anterior blepharitis involves the eyelid skin and eyelashes, while the posterior type affects the meibomian glands. Often, these conditions overlap. Blepharitis
  • Iritis Iritis Inflammation of the iris characterized by circumcorneal injection, aqueous flare, keratotic precipitates, and constricted and sluggish pupil along with discoloration of the iris. Leprosy
  • Keratitis Keratitis Inflammation of the cornea. Herpes Simplex Virus 1 and 2
  • Chalazion Chalazion A chalazion is one of the most common inflammatory lesions of the eyelid. It is caused by obstruction of the Meibomian or Zeis glands, leading to granulomatous inflammation and resulting in a firm, rubbery, slow-growing nodule that is typically non-tender. Chalazion or hordeola
  • Lid margin telangiectasia Telangiectasia Permanent dilation of preexisting blood vessels creating small focal red lesions, most commonly in the skin or mucous membranes. It is characterized by the prominence of skin blood vessels, such as vascular spiders. Chronic Venous Insufficiency
  • Dry, burning, or stinging sensations
  • Light sensitivity
  • Blurred vision Blurred Vision Retinal Detachment
  • Sensation of foreign body Foreign Body Foreign Body Aspiration
• Traditional subtypes/classic phenotypes (based on common manifestations):
  • Erythematotelangiectatic
  • Papulopustular
  • Phymatous
  • Ocular
• Characteristics:
  • Periods of remission Remission A spontaneous diminution or abatement of a disease over time, without formal treatment. Cluster Headaches and exacerbation of symptoms
  • Associated with a number of systemic inflammatory disorders:
    • Cardiovascular
    • Gastrointestinal
    • Neurologic
    • Autoimmune

Management and Prognosis

General measures^[4,5]

• Identify and avoid triggers
• Broad-spectrum Broad-Spectrum Fluoroquinolones ultraviolet protection
• Gentle skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions cleansing
• Keep skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions moisturized.
• Avoid irritating topical products and exfoliation.
• Consider the need for psychological support in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder or depression related to their symptoms.
• Consider specialist consultation if not responsive to topical therapies.

Therapy for erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion and flushing^[3,4]

• Topical agents (induce and maintain remission Remission A spontaneous diminution or abatement of a disease over time, without formal treatment. Cluster Headaches):
  • Brimonidine Brimonidine Rosacea: Apply a pea-sized amount over the entire face once daily.
  • Oxymetazoline Oxymetazoline A direct acting sympathomimetic used as a vasoconstrictor to relieve nasal congestion. Rosacea: Apply a pea-sized amount over the entire face once daily.
  • Retinoids Retinoids Retinol and derivatives of retinol that play an essential role in metabolic functioning of the retina, the growth of and differentiation of epithelial tissue, the growth of bone, reproduction, and the immune response. Dietary vitamin A is derived from a variety of carotenoids found in plants. It is enriched in the liver, egg yolks, and the fat component of dairy products. Fat-soluble Vitamins and their Deficiencies may also be used in combination with other therapies.
• Laser therapy Laser Therapy The use of photothermal effects of lasers to coagulate, incise, vaporize, resect, dissect, or resurface tissue. Glaucoma to reduce telangiectasia Telangiectasia Permanent dilation of preexisting blood vessels creating small focal red lesions, most commonly in the skin or mucous membranes. It is characterized by the prominence of skin blood vessels, such as vascular spiders. Chronic Venous Insufficiency:
  • Intense pulsed light
  • Pulsed dye laser
  • Neodymium-doped yttrium aluminum garnet (Nd:YAG) laser
• Avoid steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors (as they may worsen the condition).
• Consider propranolol Propranolol A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for myocardial infarction; arrhythmia; angina pectoris; hypertension; hyperthyroidism; migraine; pheochromocytoma; and anxiety but adverse effects instigate replacement by newer drugs. Antiadrenergic Drugs for flushing.

Therapy for pustules and papules^[3‒5]

Topical treatments (1st-line agents):

• Ivermectin Ivermectin A mixture of mostly avermectin h2b1a (rn 71827-03-7) with some avermectin h2b1b (rn 70209-81-3), which are macrolides from streptomyces avermitilis. It binds glutamate-gated chloride channel to cause increased permeability and hyperpolarization of nerve and muscle cells. It also interacts with other chloride channels. It is a broad spectrum antiparasitic that is active against microfilariae of onchocerca volvulus but not the adult form. Anthelmintic Drugs (cream): apply to the affected area once daily
• Metronidazole Metronidazole A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. Pyogenic Liver Abscess:
  • 1% preparation: apply to affected area once daily OR
  • 0.75% preparation: twice daily 
• Azelaic acid Azelaic Acid Acne Vulgaris 15% (gel or foam): apply a thin film to the affected areas twice daily
• Sulfacetamide 10%–sulfur 5% (cream, gel, cleanser, topical suspension)
• Minocycline Minocycline A tetracycline analog, having a 7-dimethylamino and lacking the 5 methyl and hydroxyl groups, which is effective against tetracycline-resistant staphylococcus infections. Tetracyclines 1.5% (foam): Apply to affected area once daily.

Oral antibiotics: 

• Can be used as 1st-line agents in severe cases
• Best option (strongest evidence): doxycycline
  • Subantimicrobial dosing: 40 mg delayed-release tablets once daily or 20 mg immediate-release tablets twice daily
  • Traditional dosing: 50‒10 mg twice daily for 4‒12 weeks 
• Other options:
  • Azithromycin Azithromycin A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Macrolides and Ketolides
  • Trimethoprim Trimethoprim The sulfonamides are a class of antimicrobial drugs inhibiting folic acid synthesize in pathogens. The prototypical drug in the class is sulfamethoxazole. Although not technically sulfonamides, trimethoprim, dapsone, and pyrimethamine are also important antimicrobial agents inhibiting folic acid synthesis. The agents are often combined with sulfonamides, resulting in a synergistic effect. Sulfonamides and Trimethoprim– sulfamethoxazole Sulfamethoxazole A bacteriostatic antibacterial agent that interferes with folic acid synthesis in susceptible bacteria. Its broad spectrum of activity has been limited by the development of resistance. Sulfonamides and Trimethoprim
  • Minocycline Minocycline A tetracycline analog, having a 7-dimethylamino and lacking the 5 methyl and hydroxyl groups, which is effective against tetracycline-resistant staphylococcus infections. Tetracyclines
  • Tetracycline Tetracycline A naphthacene antibiotic that inhibits amino Acyl tRNA binding during protein synthesis. Drug-Induced Liver Injury
• Duration:
  • Optimal duration is unknown.
  • Attempt to avoid long-term use if possible.
  • A lack of response in 2‒3 months may be considered treatment failure.

Isotretinoin:

• May be used in people with persistent severe disease
• Should be given at low dose: 0.25 mg/kg
• Appropriate monitoring is required:
  • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care avoidance in women (teratogenic)
  • Lipid testing

Therapy for phymatous changes^[3,4]

• Isotretinoin
• Nasal debulking, which may be accomplished via:
  • Laser ablation
  • Surgery

Ocular therapy^[3,4,11]

• Ophthalmologists should evaluate patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.
• General ocular measures:
  • Avoid aggravating factors:
    • Air conditioning or excessive central heat Heat Inflammation
    • Smoke
    • Periocular cosmetics
  • Increase humidity to reduce tear evaporation.
  • If possible, attempt to modify systemic medications that may cause dry eyes, such as antidepressants.
  • Warm compresses Warm Compresses Chalazion
  • Commercially available lid wipes
• Artificial tears
• Topical antibiotics:
  • Cyclosporin
  • Azithromycin Azithromycin A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Macrolides and Ketolides
  • Erythromycin Erythromycin A bacteriostatic antibiotic macrolide produced by streptomyces erythreus. Erythromycin a is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50s ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. Macrolides and Ketolides
  • Metronidazole Metronidazole A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. Pyogenic Liver Abscess
• Oral antibiotics:
  • Cyclosporin
  • Azithromycin Azithromycin A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Macrolides and Ketolides
  • Doxycycline (subantimicrobial dosing)
  • Metronidazole Metronidazole A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. Pyogenic Liver Abscess

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas^[8,9]

• Rosacea Rosacea Rosacea is a chronic inflammatory disease of the skin that is associated with capillary hyperreactivity. This condition is predominantly seen in middle-aged women, and is more common in fair-skinned patients. Rosacea is a lifelong condition and requires long-term care.
• Rosacea Rosacea Rosacea is a chronic inflammatory disease of the skin that is associated with capillary hyperreactivity. This condition is predominantly seen in middle-aged women, and is more common in fair-skinned patients. Rosacea is not a life-threatening condition.
• If untreated, permanent scarring Scarring Inflammation can develop.
• Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may develop anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder or depression.

Differential Diagnosis

• Acne vulgaris Acne vulgaris Acne vulgaris, also known as acne, is a common disorder of the pilosebaceous units in adolescents and young adults. The condition occurs due to follicular hyperkeratinization, excess sebum production, follicular colonization by Cutibacterium acnes, and inflammation. Acne Vulgaris: the most common skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions disease, which results from obstruction and inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of hair follicles and sebaceous glands. Acne can present as open (or closed) comedones Comedones Acne Vulgaris, papules, pustules, nodules, or cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change. The diagnosis is clinical. Management depends on the severity and may include topical therapies, antibiotics, and retinoids Retinoids Retinol and derivatives of retinol that play an essential role in metabolic functioning of the retina, the growth of and differentiation of epithelial tissue, the growth of bone, reproduction, and the immune response. Dietary vitamin A is derived from a variety of carotenoids found in plants. It is enriched in the liver, egg yolks, and the fat component of dairy products. Fat-soluble Vitamins and their Deficiencies.
• Seborrheic dermatitis Dermatitis Any inflammation of the skin. Atopic Dermatitis (Eczema): a common chronic, relapsing skin disorder Relapsing Skin Disorder Seborrheic Dermatitis that presents as erythematous plaques with greasy yellow scales Scales Dry or greasy masses of keratin that represent thickened stratum corneum. Secondary Skin Lesions in susceptible areas (scalp, face, and trunk). This condition can be seen in the nasolabial folds. The diagnosis is clinical. Steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors, calcineurin inhibitors Calcineurin Inhibitors Compounds that inhibit or block the phosphatase activity of calcineurin. Immunosuppressants, and antifungal Antifungal Azoles agents are used in the management of this condition.
• Systemic lupus erythematosus Systemic lupus erythematosus Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus ( SLE SLE Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus): a chronic, autoimmune, multisystem, inflammatory condition. Cutaneous findings can include a malar rash Malar Rash Systemic Lupus Erythematosus (which spares the nasolabial folds). Multiple systemic symptoms may also be present, including arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis, nephritis, serositis Serositis Inflammation of a serous membrane. Systemic Lupus Erythematosus, cytopenia, thromboembolic disease, seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures, and/or psychosis. The diagnosis is made by meeting clinical criteria, which include antinuclear and SLE-specific antibodies SLE-specific antibodies Systemic Lupus Erythematosus. Management involves corticosteroids Corticosteroids Chorioretinitis, hydroxychloroquine Hydroxychloroquine A chemotherapeutic agent that acts against erythrocytic forms of malarial parasites. Hydroxychloroquine appears to concentrate in food vacuoles of affected protozoa. It inhibits plasmodial heme polymerase. Immunosuppressants, and immunosuppressants Immunosuppressants Immunosuppressants are a class of drugs widely used in the management of autoimmune conditions and organ transplant rejection. The general effect is dampening of the immune response. Immunosuppressants.