Grand Rounds at the New England Eye Center

Woman experiences foreign body sensation in right eye

There was a small, nodular, umbilicated lesion on the medial right upper eyelid.

A 36-year-old woman presented to the New England Eye Center with 2 months of redness, irritation and foreign body sensation in her right eye worse than the left. She had no significant ocular history other than mild myopia. Her medical history included HELLP syndrome with a prior pregnancy and chlamydial cervicitis and urethritis 15 years prior treated with antibiotics.

Examination

On examination, the patient’s visual acuity was 20/20 in each eye. Her pupillary exam, extraocular motility and IOP were within normal limits. Anterior segment exam revealed moderate meibomian gland inspissation, diffuse 1+ conjunctival injection in the right eye and trace injection in the left, with moderately sized follicles more abundant in the right inferior fornix and palpebral conjunctiva than in the left (Figure 1). Closer examination of the periocular skin revealed a small, nodular, umbilicated lesion on the medial right upper eyelid (Figure 2). No significant discharge was noted. Her corneas were clear, and the rest of her slit lamp exam, including dilated fundus exam, was unremarkable.

Inferior fornix of the right eye showing conjunctival injection and follicles.  

Figure 1. Inferior fornix of the right eye showing conjunctival injection and follicles. Inspissated meibomian glands are also noted.

Images: Sitko K, Hu D

A small, nodular, umbilicated lesion was visible on the right upper eyelid. 

Figure 2. A small, nodular, umbilicated lesion was visible on the right upper eyelid.

 

What is your diagnosis?
Chronic Conjuntivitis

The patient was exhibiting an asymmetric chronic follicular conjunctivitis. The differential diagnosis for chronic conjunctivitis in general includes infectious, allergic, mechanical, inflammatory and neoplastic etiologies.

The major infectious causes include Chlamydia trachomatis, Staphylococcus, Moraxella, Bartonella (Parinaud’s oculoglandular syndrome), Borrelia burgdorferi (Lyme disease), Microsporidia and molluscum contagiosum. Mechanical causes include poorly fitting or inappropriately worn contact lenses and floppy eyelid syndrome. Examples of primary inflammatory causes are rosacea and chronic conjunctivitis associated with HLA-B27 and reactive arthritis. Although most cases of conjunctival lymphoma are manifested as focal “salmon patches,” there have been case reports of biopsy-proven lymphoma diagnosed in difficult-to-treat cases of chronic diffuse conjunctivitis.

The differential diagnosis of follicular conjunctivitis is more limited to infectious etiologies. These include adenovirus, herpes simplex virus (HSV), molluscum contagiosum and Chlamydia trachomatis. Of these, adenovirus- and HSV-associated conjunctivitis are usually more acute in their course. The overlap between the two differentials described above includes Chlamydia trachomatis and molluscum contagiosum. Notably, our patient denied itching, was not a contact lens wearer, and exhibited no evidence of rosacea or floppy eyelids.

Diagnosis

In this case, suspicion was high for an infectious cause. Given the patient’s history of chlamydia venereal infection, conjunctival scrapings were sent, but they were negative for Chlamydia trachomatis. Routine cultures were also sent and were negative for fungus, adenovirus and HSV.

On follow-up, the patient was noted to have multiple nodular, umbilicated skin lesions on her lids, forehead and just beneath the nose. Because they appeared suspicious for molluscum contagiosum, all five lesions were excised and sent for pathology. These slides showed the classic findings of molluscum lesions: crater shaped with hypertrophied lobules of epidermis projecting into the dermis (Figure 3). Visible were intracytoplasmic inclusion bodies in the stratum spinosum (Henderson-Paterson bodies) that usually increase in size as the cells move toward the surface and crowd out the normal cellular material. Once the Henderson-Paterson bodies emerge to the surface of the crater floor, they are known to break through and be released along with desquamated keratin onto the ocular surface.

Hematoxylin and eosin stain of the right upper eyelid lesion 

Figure 3. Hematoxylin and eosin stain of the right upper eyelid lesion showed a crater-shaped nodular lesion with hypertrophied lobules of epidermis penetrating into the underlying dermis with intracytoplasmic inclusion bodies.

 

Discussion and management

Molluscum contagiosum is caused by a double-stranded DNA virus that is a member of the poxvirus family. There are two forms of disease based on the population affected. The childhood form is transmitted by skin-to-skin contact and fomite-to-skin contact. The lesions in the childhood form are commonly found on the face, trunk and limbs. In young adults, the transmission is by skin contact associated with sexual intercourse. The lesions are primarily seen in the genital area. Studies supporting the disease as a sexually transmitted infection demonstrate identification of lesions in sexual partners, common occurrence on the genitals and common concurrence of other sexually transmitted infections in the affected population. In populations that are immunosuppressed, particularly in patients with AIDS, the lesions can be larger, appear in greater number and be harder to control.

Periocular manifestations are common and most often manifest as lesions on the eyelid. They can be associated with follicular conjunctivitis and also punctate keratopathy and subepithelial keratitis. Conjunctival lesions have also been reported.

Untreated, these lesions can last from 6 months to 3 years but ultimately resolve without treatment. Watchful waiting is the most common treatment, but intervention is often necessary when associated with secondary symptoms such as conjunctivitis. The most common treatment is curettage. It has shown to be effective, but multiple treatment sessions are often necessary for complete resolution due to subclinical lesions. The number of lesions at initial presentation has also been correlated with failure of curettage as a treatment modality. In addition to curettage, other destructive methods of molluscum contagiosum lesions include cryotherapy; topical potassium hydroxide, which works through keratolysis and destruction of the skin; and cantharidin, which is a topical vesicant acquired from blister beetles. Other treatment options include immunologic methods and antivirals. Imiquimod is an immunologic agent that works through induction of IFN-alpha, TNF-alpha and cell-mediated immunity. Cidofovir is an antiviral medication reported to improve recalcitrant molluscum contagiosum lesions in patients with HIV.

Follow-up

After her initial excision, the patient returned for follow-up and was found to have persistent symptoms and several new skin lesions. These were also excised. At her most recent follow-up appointment, the patient was both symptom- and lesion-free.

References:
Akpek EK, Polcharoen W, Ferry JA, Foster CS. Conjunctival lymphoma masquerading as chronic conjunctivitis. Ophthalmology. 1999;106(4):757-760.
Brown ST, Nalley JF, Kraus SJ. Molluscum contagiosum. Sex Transm Dis. 1981;8(3):227-234.
Coloe Dosal J, Stewart PW, Lin JA, Williams CS, Morrell DS. Cantharidin for the treatment of molluscum contagiosum: a prospective, double-blinded, placebo-controlled trial [published online ahead of print Aug. 16, 2012]. Pediatr Dermatol. 2012;doi: 10.1111/j.1525-1470.2012.01810.x.
Meadows KP, Tyring SK, Pavia AT, Rallis TM. Resolution of recalcitrant molluscum contagiosum virus lesions in human immunodeficiency virus-infected patients treated with cidofovir. Arch Dermatol. 1997;133(8):987-990.
Schornack MM, Siemsen DW, Bradley EA, Salomao DR, Lee HB. Ocular manifestations of molluscum contagiosum. Clin Exp Optom. 2006;89(6):390-393.
Seo SH, Chin HW, Jeong DW, Sung HW. An open, randomized, comparative clinical and histological study of imiquimod 5% cream versus 10% potassium hydroxide solution in the treatment of molluscum contagiosum. Ann Dermatol. 2010;22(2):156-162.
Simonart T, De Maertelaer V. Curettage treatment for molluscum contagiosum: a follow-up survey study. Br J Dermatol. 2008;159(5):1144-1147.
For more information:
Kevin Sitko, MD, and Daniel Hu, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.
Edited by Kavita Bhavsar, MD, and Michelle C. Liang, MD. They can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.

A 36-year-old woman presented to the New England Eye Center with 2 months of redness, irritation and foreign body sensation in her right eye worse than the left. She had no significant ocular history other than mild myopia. Her medical history included HELLP syndrome with a prior pregnancy and chlamydial cervicitis and urethritis 15 years prior treated with antibiotics.

Examination

On examination, the patient’s visual acuity was 20/20 in each eye. Her pupillary exam, extraocular motility and IOP were within normal limits. Anterior segment exam revealed moderate meibomian gland inspissation, diffuse 1+ conjunctival injection in the right eye and trace injection in the left, with moderately sized follicles more abundant in the right inferior fornix and palpebral conjunctiva than in the left (Figure 1). Closer examination of the periocular skin revealed a small, nodular, umbilicated lesion on the medial right upper eyelid (Figure 2). No significant discharge was noted. Her corneas were clear, and the rest of her slit lamp exam, including dilated fundus exam, was unremarkable.

Inferior fornix of the right eye showing conjunctival injection and follicles.  

Figure 1. Inferior fornix of the right eye showing conjunctival injection and follicles. Inspissated meibomian glands are also noted.

Images: Sitko K, Hu D

A small, nodular, umbilicated lesion was visible on the right upper eyelid. 

Figure 2. A small, nodular, umbilicated lesion was visible on the right upper eyelid.

 

What is your diagnosis?
Chronic Conjuntivitis

The patient was exhibiting an asymmetric chronic follicular conjunctivitis. The differential diagnosis for chronic conjunctivitis in general includes infectious, allergic, mechanical, inflammatory and neoplastic etiologies.

The major infectious causes include Chlamydia trachomatis, Staphylococcus, Moraxella, Bartonella (Parinaud’s oculoglandular syndrome), Borrelia burgdorferi (Lyme disease), Microsporidia and molluscum contagiosum. Mechanical causes include poorly fitting or inappropriately worn contact lenses and floppy eyelid syndrome. Examples of primary inflammatory causes are rosacea and chronic conjunctivitis associated with HLA-B27 and reactive arthritis. Although most cases of conjunctival lymphoma are manifested as focal “salmon patches,” there have been case reports of biopsy-proven lymphoma diagnosed in difficult-to-treat cases of chronic diffuse conjunctivitis.

The differential diagnosis of follicular conjunctivitis is more limited to infectious etiologies. These include adenovirus, herpes simplex virus (HSV), molluscum contagiosum and Chlamydia trachomatis. Of these, adenovirus- and HSV-associated conjunctivitis are usually more acute in their course. The overlap between the two differentials described above includes Chlamydia trachomatis and molluscum contagiosum. Notably, our patient denied itching, was not a contact lens wearer, and exhibited no evidence of rosacea or floppy eyelids.

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Diagnosis

In this case, suspicion was high for an infectious cause. Given the patient’s history of chlamydia venereal infection, conjunctival scrapings were sent, but they were negative for Chlamydia trachomatis. Routine cultures were also sent and were negative for fungus, adenovirus and HSV.

On follow-up, the patient was noted to have multiple nodular, umbilicated skin lesions on her lids, forehead and just beneath the nose. Because they appeared suspicious for molluscum contagiosum, all five lesions were excised and sent for pathology. These slides showed the classic findings of molluscum lesions: crater shaped with hypertrophied lobules of epidermis projecting into the dermis (Figure 3). Visible were intracytoplasmic inclusion bodies in the stratum spinosum (Henderson-Paterson bodies) that usually increase in size as the cells move toward the surface and crowd out the normal cellular material. Once the Henderson-Paterson bodies emerge to the surface of the crater floor, they are known to break through and be released along with desquamated keratin onto the ocular surface.

Hematoxylin and eosin stain of the right upper eyelid lesion 

Figure 3. Hematoxylin and eosin stain of the right upper eyelid lesion showed a crater-shaped nodular lesion with hypertrophied lobules of epidermis penetrating into the underlying dermis with intracytoplasmic inclusion bodies.

 

Discussion and management

Molluscum contagiosum is caused by a double-stranded DNA virus that is a member of the poxvirus family. There are two forms of disease based on the population affected. The childhood form is transmitted by skin-to-skin contact and fomite-to-skin contact. The lesions in the childhood form are commonly found on the face, trunk and limbs. In young adults, the transmission is by skin contact associated with sexual intercourse. The lesions are primarily seen in the genital area. Studies supporting the disease as a sexually transmitted infection demonstrate identification of lesions in sexual partners, common occurrence on the genitals and common concurrence of other sexually transmitted infections in the affected population. In populations that are immunosuppressed, particularly in patients with AIDS, the lesions can be larger, appear in greater number and be harder to control.

Periocular manifestations are common and most often manifest as lesions on the eyelid. They can be associated with follicular conjunctivitis and also punctate keratopathy and subepithelial keratitis. Conjunctival lesions have also been reported.

Untreated, these lesions can last from 6 months to 3 years but ultimately resolve without treatment. Watchful waiting is the most common treatment, but intervention is often necessary when associated with secondary symptoms such as conjunctivitis. The most common treatment is curettage. It has shown to be effective, but multiple treatment sessions are often necessary for complete resolution due to subclinical lesions. The number of lesions at initial presentation has also been correlated with failure of curettage as a treatment modality. In addition to curettage, other destructive methods of molluscum contagiosum lesions include cryotherapy; topical potassium hydroxide, which works through keratolysis and destruction of the skin; and cantharidin, which is a topical vesicant acquired from blister beetles. Other treatment options include immunologic methods and antivirals. Imiquimod is an immunologic agent that works through induction of IFN-alpha, TNF-alpha and cell-mediated immunity. Cidofovir is an antiviral medication reported to improve recalcitrant molluscum contagiosum lesions in patients with HIV.

Follow-up

After her initial excision, the patient returned for follow-up and was found to have persistent symptoms and several new skin lesions. These were also excised. At her most recent follow-up appointment, the patient was both symptom- and lesion-free.

References:
Akpek EK, Polcharoen W, Ferry JA, Foster CS. Conjunctival lymphoma masquerading as chronic conjunctivitis. Ophthalmology. 1999;106(4):757-760.
Brown ST, Nalley JF, Kraus SJ. Molluscum contagiosum. Sex Transm Dis. 1981;8(3):227-234.
Coloe Dosal J, Stewart PW, Lin JA, Williams CS, Morrell DS. Cantharidin for the treatment of molluscum contagiosum: a prospective, double-blinded, placebo-controlled trial [published online ahead of print Aug. 16, 2012]. Pediatr Dermatol. 2012;doi: 10.1111/j.1525-1470.2012.01810.x.
Meadows KP, Tyring SK, Pavia AT, Rallis TM. Resolution of recalcitrant molluscum contagiosum virus lesions in human immunodeficiency virus-infected patients treated with cidofovir. Arch Dermatol. 1997;133(8):987-990.
Schornack MM, Siemsen DW, Bradley EA, Salomao DR, Lee HB. Ocular manifestations of molluscum contagiosum. Clin Exp Optom. 2006;89(6):390-393.
Seo SH, Chin HW, Jeong DW, Sung HW. An open, randomized, comparative clinical and histological study of imiquimod 5% cream versus 10% potassium hydroxide solution in the treatment of molluscum contagiosum. Ann Dermatol. 2010;22(2):156-162.
Simonart T, De Maertelaer V. Curettage treatment for molluscum contagiosum: a follow-up survey study. Br J Dermatol. 2008;159(5):1144-1147.
For more information:
Kevin Sitko, MD, and Daniel Hu, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.
Edited by Kavita Bhavsar, MD, and Michelle C. Liang, MD. They can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.