International Journal of Dermatology

2008,

47

, 1304–1305 © 2008

The International Society of Dermatology

1304

A 43-year-old white man with molluscum contagiosum and a history of Wiskott–Aldrich

syndrome presented to our clinic. He had previously finished six cycles of chemotherapy

with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone),

and had achieved complete remission for diffuse large B-cell lymphoma.

The patient had a 1.5-year history of molluscum contagiosum that had spread to the entire

trunk and upper and lower extremities. Past therapies included liquid nitrogen cryotherapy,

imiquimod, cantharidin, curettage, topical emollients (Dermasil), salicylic acid (Clear Away

and Compound W), and trichloroacetic acid peel. Most recently, topical cidofovir had resulted

in severe edema of the left arm.

On physical examination, the patient had hundreds of umbilicated, flesh-colored to

erythematous papules over his body(Figs 1 and 2). A lesional biopsy of a 5-mm umbilicated

papule from the left axilla showed epidermal cells and infundibular hair follicles with large

intracytoplasmic molluscum inclusion bodies.

Laboratory results included a normal metabolic panel, complete blood count (CBC),

and liver function tests (LFTs), as well as a negative human immunodeficiency virus (HIV) test.

The patient’s immunoglobulin E (IgE), IgG, and IgA were all normal. However, abnormally

low laboratory values included an IgM of 17 mg/dL and absolute CD4 and CD8 counts

of 203 and 41

μ

L, respectively.

Initial therapy included topical imiquimod and oral acitretin 25 mg daily. Three months later,

the patient showed slight improvement only and acitretin was discontinued. He had also been

using salicylic acid (Compound W) and silver nitrate applications. Most recently, the plan

included continuation of cantharidin toothpick treatment and imiquimod, and the potential

addition of systemic interferons (

γ

or

α

) and topical or intravenous cidofovir.

Blackwell Publishing LtdOxford, UKIJDInternational Journal of Dermatology0011-90591365-4632Blackwell Publishing Ltd, 2008XXX

Pharmacology and therapeutics

Wiskott-Aldrich and molluscum contagiosum

Hicks and Duvic

Pharmacology and therapeutics

Wiskott–Aldrich syndrome and molluscum contagiosum: a therapeutic challenge after reaction to cidofovir

Lindsey D. Hicks,

BS

, and Madeleine Duvic,

MD

From the Department of Dermatology, University of Texas-Houston Health Science Center and University of Texas M.D. Anderson Cancer Center, Houston, Texas

Correspondence

Lindsey D. Hicks,

BS

1885 El Paseo Street, Apartment #515 Houston, TX 77054 E-mail: Lindsey.d.hicks@uth.tmc.edu

Discussion

Molluscipoxvirus is an epitheliotropic double-stranded DNAvirus that is a member of the Poxviridae family.

1

In immuno-compromised patients and those with human immuno-deficiency virus (HIV), its prevalence is estimated to be ashigh as 18%.

2,3

Wiskott–Aldrich syndrome, an X-linked dis-order of eczema, thrombocytopenia, autoimmune dysfunction,malignancies, and infections, is caused by mutations inthe

Wiskott–Aldrich syndrome protein

(

WASP

) gene. WASPplays an important role in the organization of cytoskeletalelements, signal transduction, and the development of platelets,and T and B cells.

4–6

The immune dysfunction of Wiskott–Aldrich syndromecreates a unique situation in which molluscum contagiosumhas the potential to disseminate.

7

The viral CC chemokine

functions to inhibit leukocyte migration and monocytefunction. The major histocompatibility complex-1 (MHC-1)homolog interferes with molluscum contagiosum virus (MCV)antigen presentation by Langerhans antigen-presentingcells (APCs). A glutathione peroxidase analog and caspase8 inhibitor prevent cell surface death receptor interaction andreactive oxygen species-induced death. The

WASP

genemutation creates dysfunction in the actin cytoskeleton that iscrucial for immune cells to grow, differentiate, localize, andundergo adhesion and migration. WASP-induced cytoskeletaldysfunction prevents natural killer cell production ofinterferon-

γ

, a cytokine that has important antiviral,antitumor, and immunoregulatory functions.

5,6,8

In immunocompromised patients, many of the traditionaldestructive methods of therapy fail to produce completeresolution because of a lack of an immune response to the

© 2008

The International Society of Dermatology International Journal of Dermatology

2008,

47

, 1304–1305

1305

Hicks and Duvic

Wiskott-Aldrich and molluscum contagiosum

Pharmacology and therapeutics

released viral antigens.

1,2,7,9

Subcutaneous interferon-

α

hasbeen used successfully in children with combined immuno-deficiency, reduced IgM, and lymphocytopenia.

10

Cimetidinehas been used as a result of its proliferative effect on lym-phocytes and inhibition of suppressor T-cell function.

11,12

Amember of the depsipeptides, sansalvamide A, is a naturalmarine fungal molecule that enhances the immune systemand inhibits a viral topoisomerase that is required for replica-tion.

7

Finally, combination therapy is recommended to syner-gistically increase the response rate and time to resolution.

Combination CO

2

laser and topical interferon-

β

gel has beenused in patients with acquired immunodeficiency syndrome(AIDS) and recalcitrant MCV.

13

Treatment-resistant, disseminated MCV is disfiguringand frustrating. Immunocompromised patients with dis-seminated MCV frequently do not respond to destructivetreatments, and may require combination therapy that is bothantiviral and immunomodulating.

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Figure 1 Disseminated molluscum-lower back

Figure 2 Disseminated molluscum-upper chest