Ocular manifestations of infectious skin diseases

    Ocular manifestations of infectious skin diseases Anna Sadowska–Przytocka MD, Magdalena Czarnecka–Operacz MD, PhD, Dorota Jenerowicz MD, PhD, Andrzej Grzybowski MD, PhD PII: DOI: Reference:

S0738-081X(15)00235-7 doi: 10.1016/j.clindermatol.2015.11.010 CID 7005

To appear in:

Clinics in Dermatology

Please cite this article as: Sadowska–Przytocka Anna, Czarnecka–Operacz Magdalena, Jenerowicz Dorota, Grzybowski Andrzej, Ocular manifestations of infectious skin diseases, Clinics in Dermatology (2015), doi: 10.1016/j.clindermatol.2015.11.010

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ACCEPTED MANUSCRIPT Ocular manifestations of infectious skin diseases Anna Sadowska – Przytocka

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MD, Magdalena Czarnecka – Operacz

Professor of Dermatology, Dorota Jenerowicz

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MD, PhD,

MD, PhD, Andrzej Grzybowski

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MD, PhD, Professor of Ophthalmology

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1 Department of Dermatology, Poznan University of Medical Sciences, Poland

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2 Department of Ophthalmology, Poznan City Hospital, Poland

Corresponding author: Anna Sadowska – Przytocka MD

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3 Department of Ophthalmology, University of Warmia and Mazury, Olsztyn, Poland

Przybyszewskiego 49

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60-355 Poznań, Poland

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Department of Dermatology, Poznan University of Medical Sciences, Poland

Abstract

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[email protected]

Ocular complications of infectious skin diseases are a frequent occurrence. Managing the inflamed or infected eye in the emergency setting presents a diagnostic and therapeutic challenge to the emergency physician. Infectious agents may affect any part of the eye. Ocular findings may be the first sign of many infectious diseases, as for example gonorrhea or Chlamydia infection. Understanding the various forms of ocular involvement in these conditions is important, as untreated ophthalmic involvement can lead to severe vision loss. This review focuses on the significant ocular manifestations of the most common infectious diseases including bacterial, viral, fungal, and parasitic infections that both ophthalmologists and dermatologists may encounter.

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ACCEPTED MANUSCRIPT Key words: infectious skin diseases, eye, infectious agents

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Introduction

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Infectious diseases of the skin and sexually transmitted diseases (STDs) often affect not only the skin but also other organs and systems. Ocular findings may be

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the first of many infectious diseases. Ocular infection may be the primary infection as with gonorrhea and Chlamydia infection, or secondary as in case of acquired immune deficiency syndrome (AIDS). This review focuses on the significant ocular

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manifestations of the most common infectious diseases including bacterial, viral, fungal, and parasitic infections confronting both ophthalmologists and dermatologists.

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Bacterial diseases

Staphylococcal species are the most common causative organism in hordeolum (1). A hordeolum represents purulent infection of a cilium and the adjacent gland with the

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local formation of an abscess. Cellulitis may accompany the hordeolum. Treatment includes warm compresses several times a day for 10 minutes. To prevent local

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complications, topical antibiotics are also used.

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Chalazions are granulomatous inflammatory lesions present on the lid, which occur from obstruction of the sebaceous gland. Clinically, they are often indistinguishable from a hordeolum. They may resolve spontaneously as does a hordeolum. Recurrent chalazions require an ophthalmologic referral for a possible biopsy and evaluation to rule out malignancy (2). Erysipelas (Fig. 1, 2) is usually caused by group A β-hemolytic Streptococci, but similar lesions can be caused by group B, C and G Streptococci and less often by Staphylococci,

Haemophilus

influenzae,

Pseudomonas

aeruginosa,

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Enterobacteria. The diagnosis is based on such classic clinical findings as a fiery red, tender, painful plaque with well-demarcated edges. Erysipelas classically involves the face, but currently the predominant location is the lower extremities. General symptoms and signs such as fever, chills, and malaise, together with regional lymphadenopathy, and laboratory findings including leukocytosis, elevated C-reactive 2

ACCEPTED MANUSCRIPT protein or erythrocyte sedimentation rate are, usually present. Penicillin is the empiric antibiotic of choice, while macrolides are usually recommended in patients allergic to penicillin (3).

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Chlamydia trachomatis is the most commonly reported bacterial STD in the USA (4).

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Chlamydial conjunctivitis is a STD, occurring most commonly in sexually active young adults. Autoinoculation is considered to be the main route of transmission. Swimming

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pools, insects, and other fomites may act as vectors (5). Adult inclusion conjunctivitis is caused by serotypes D-K. Ocular signs include red eye with stringy discharge, including conjuncitival injection, superficial punctate keratitis, superior corneal

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pannus, peripheral subepithelial infiltrates, iritis, and follicles. A palpable preauricular node is almost always observed. Chlamydial conjunctivitis is often a unilateral infection but can involve both eyes. Conventional diagnostic procedures are cell culture and direct immunofluorescent assay. Polymerase chain reaction (PCR) may be helpful for incipient infection (5). Untreated chlamydial conjunctivitis resolves

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spontaneously in 6-8 months. Systemic antibiotic therapy with tetracycline or a macrolide is the mainstay treatment. Topically, tetracycline, erythromycin, or

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ciprofloxacin can be used (4).

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Gonorrhea is the second most common bacterial STD after chlamydia in the USA (4). The usual clinical manifestations in men are burning with urination and penile discharge. 50 % of women are either asymptomatic or have vaginal discharge and

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pelvic pain (pelvic inflammatory disease). Ocular infection with Neisseria gonorrhea (N. gonorrhea) is usually transmitted by autoinoculation or direct inoculation from genital secretions of an infected partner. The disease includes red eye, profuse discharge, and lid swelling. The adult conjunctiva is especially susceptible to infection by N. gonorrhea. The main diagnostic procedures are bacterial culture and PCR. Treatment options include cephalosporins or fluoroquinolones in a single dose. For eye infections, topical antibiotics achieve much higher concentration in infected tissues than do systemic treatments (6). Ocular syphilis is uncommon. Treponema pallidum (T. pallidum) spreads to the eye via the hematogenous route. Ocular syphilis is caused either by the direct invasion by T. pallidum or by an allergic reaction in tissues sensitized by the pathogen. The ocular manifestation can occur at any stage of the disease. Syphilis can affect the 3

ACCEPTED MANUSCRIPT conjunctiva, sclera, cornea, lens, uveal tract, retina, retinal vasculature, optic nerve, pupillomotor pathways, and cranial nerves involved in extra ocular movements. The most common ocular sign of syphilis is uveitis. It can occur 6 weeks after primary

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infection. The ocular inflammation may be granulomatous or non-granulomatous and

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may involve the anterior segment, posterior segment, or both. The classic pupillary finding in syphilis is Argyll Robertson pupil, including bilateral small pupils with light dissociation (they accommodate but do not react) (7). The diagnosis of syphilis is

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based on clinical presentation and is supported by serologic testing. Parenterally administrated benzathine penicillin is the drug of choice for the treatment of all stages

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of syphilis (4, 8). Viral diseases

Molluscum contagiosum (Fig. 3) is commonly observed in children, sexually active adults, and immunosuppressed patients during therapy with TNFα antibodies,

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methotrexate, and steroids (9). Molluscum contagiosum are discrete pearly pink, umblicated papules. The lesions are usually multiple and grouped, sometimes with

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localized surrounding eczematous dermatitis. Molluscum contagiosum may affect the eyelid, conjunctiva and even cornea (10). Although these lesions are generally self-

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limited, in patients with weakened immune systems they may persist for prolonged periods when recalcitrant disease is observed. In causes of slow natural resolution,

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imiquimod cream, cryotherapy, or curettage can be helpful (10). Verrucae are common benign cutaneous lesions caused by infection of epidermal cells with the human papillomavirus (HPV) (Fig. 4). The virus may infect epidermal cells by direct inoculation and is transmitted by touch, including sexual contact. The virus may infect the eyelid or conjunctiva, although the commonest type of warts on the face is plane or flat warts (10). The treatment includes imiquimod cream, cryotherapy, laser therapy, and topical retinoids. A new effective and safe modality for treatment of flat warts is topical 10 % zinc sulfate solution (11). Propolis may also be an effective and safe immunomodulating therapy for flat and common warts (12). Herpes simplex virus is highly contagious and is spread by direct contact. There are two types of herpes simplex virus. Type 1 (HSV 1) is more often facial, and type 2 (HSV 2) is more often genital, although this distinction is not absolute (13). Ocular manifestations of HSV 1 infection include blepharitis, conjunctivitis, infectious 4

ACCEPTED MANUSCRIPT epithelial keratitis, neurotrophic keratopathy, necrotizing stromal keratitis, immune stromal keratitis, and endothelitis (10).

The typical lesions on the skin are grouped

vesicles (Fig. 1.). The outbreak of groups of vesicles is often preceded for a few

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hours by a tingling or burning sensation. Crusts form within 24 – 48 hours, and the

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infection fades after a week. Treatment involves use of acyclovir or valacyclovir. Herpes zoster (Fig. 5, 6) represents the reactivation of the zoster – varicelliform virus

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that had been contracted many years prior to chickenpox. Pain, tenderness or paraesthesia in the dermatome may precede the eruption by 3-5 days. Erythema and grouped vesicles may become pustular and then form crusts that separate in 2-3

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weeks. Secondary bacterial infection may occur. Approximately 10-20 % of all herpes zoster presents as herpes zoster ophthalmicus (14). It may involve the eyelid, conjunctiva, sclera, cornea, or iris. There are currently three antivirals used in VZV infection: acyclovir, valacyclovir, and famciclovir. Intravenous acyclovir is the drug of

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choice in immunosuppressed patients to prevent disseminated infection. Ocular complications of Human Immunodeficiency Virus (HIV) are mainly related to

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secondary opportunistic infections, in addition to complications of antiretroviral medications. Common ocular adnexa lesions in patients with HIV include herpes

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zoster ophthalmicus (HZO), Kaposi sarcoma (caused by human herpes virus type 8), molluscum contagiosum and conjunctival microvasculopathy. More than 50 % of HIVpositive patients manifest anterior segment complications. VZV and HSV are the

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most common causes of keratitis. Iridocyclitis in HIV positive patients is often associated with retinitis due to Cytomegalovirus (CMV) or VZV. HIV retinopathy is the most common retinal pathology seen in patients with HIV. The HSV is implicated frequently in retinal and/or choroidal infections in HIV patients. CMV is the most common cause of intraocular infection in patients with AIDS. Infectious chorioiditis in HIV positive patients may be caused by Pneumocystis carini, syphilis, tuberculosis, Toxoplasma gondii, Histoplasma capsulatum, and Cryptococcus neoformans. Immune recovery uveitis (IRU) is defined as vitritis associated with complaints of floaters and/or decreased vision in patients with highly active antiretroviral therapy (HAART) mediated immune recovery and inactive CMV retinitis (15). Treatment of ocular complications of HIV and AIDS is complex. Most ocular opportunistic pathogens cannot be eradicated. Their management requires life-long suppressive therapy. 5

ACCEPTED MANUSCRIPT Fungal infections Dermatophyte infection is limited to keratinized tissue, and therefore, when the eyelid is involved, being an extension of tinea faciei often due to Microsporum canis and

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Microsporum gypseum. The eyelid is an uncommon site of infection. The lipophilic fungus Malassezia furfur - can be cultured from normal, as well as seborrheic dermatitis lesions of the eyelid, folliculitis lesions, and tinea versicolor.

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Treatment of fungal infections includes topical and systemic imidazole preparations.

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Parasitic diseases

Pthirus pubis (P. pubis) is not limited to the genitalia and may involve the eyebrows and eyelashes causing pruritus (17). Small erythematous papules with excoriation may lead to crusting of the lid margins. Diagnosis is relatively simple by microscopic scraping or direct slit lamp examination. Eyelid involvement is treated with a thick

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layer of petrolatum along the lid twice a day for 8 days; however, petrolatum does not destroy the eggs. A search should be made for crab lice in other hairy parts of the

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body, and 1% permethrin lotion is also effective, as is oral ivermectin (17). Demodex folliculorum (D. folliculorum) and Demodex brevis (D. brevis) - are the

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most common microscopic ectoparasites found in human skin. The mite lives in the hair follicles and sebaceous glands, especially of the face, nose and eyelids (18 -

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19). There is a close correlation between the severity of rosacea and Demodex blepharitis (Fig. 7, 8). It has been demonstrated that the Demodex mite can cause blepharitis by carrying bacteria on its surface, including Streptococci and Staphylococci. Superantigens produced by these bacteria are also implicated in the induction of rosacea. In various species of mites and nematodes, A Gram-negative intracellular bacterium, Wolbachia pipentis, was detected (20). Another endosporic Gram-negative bacterium, Bacillus oleronius (B. oleronius), was detected inside Demodex mites and can stimulate proliferation of peripheral blood mononuclear cell in patients with rosacea (21 - 22). The main symptoms and signs of Demodex blepharitis are itching, burning, foreign body sensation, crusting and redness of the lid margin, and blurry vision. Seborrheic dermatitis around the eyes, disorders of the eyelashes,

lid

margin

inflammation,

meibomian

gland

dysfunction,

blepharoconjuntcivitis, and blepharokeratits are observed (18). Various treatments 6

ACCEPTED MANUSCRIPT have been proposed for Demodex-associated blepharitis, including topical sulfur, mercury oxide 1 % ointment, pilocarpine gel, and camphorated oil (23). Facial Demodex infestations have been treated with topical dilute camphor oil with oral

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metronidazole (23). Treatment with tea tree oil (TTO) has resulted in alleviation of

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symptoms and a marked resolution of inflammation on the lid margin, conjunctiva ,and cornea. TTO may also exert an antibacterial and antifungal action (24).

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Ivermectin orally has also been used with some success.

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Conclusions

Ocular involvement is a common complication of infectious skin diseases. The

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correct diagnosis allows to avoid severe complications such as vision loss.

Figure legends Fig. 1. Erysipelas of face. Painful, shiny, erythematous, edematous plaques, involving eyelids and cheeks.

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ACCEPTED MANUSCRIPT Fig. 2. Erysipelas of face (Courtesy of Prof. Robert Strohal). Fig. 3. Molluscum contagiosum on the eyelid. Solid skin-colored papule, with central

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umbilication.

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Fig. 4. Flat warts on the eyelid. Multiple skin-colored papules.

Fig. 5. Varicella zoster virus infection: ophthalmic herpes zoster (Courtesy of Prof.

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Ryszard Żaba).

Fig. 6. Varicella zoster virus infection. Crusted ulcerations and vesicles on the

Fig. 7. Demodecosis

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forehead and periorbital area (Courtesy of Prof. Robert Strohal).

Fig. 8. Erythematous and edematous skin lesions localized within the skin of face (Courtesy of Dr. Daiva Jasaitiene).

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