Experience with Molluscum Contagiosum and Associated Inflammatory Reactions in a Pediatric Dermatology Practice the Bump That Rashes

STUDY

ONLINE FIRST Experience With Molluscum Contagiosum and Associated Inflammatory Reactions in a Pediatric Dermatology Practice The Bump That Rashes

Emily M. Berger, MD; Seth J. Orlow, MD, PhD; Rishi R. Patel, MD; Julie V. Schaffer, MD

Objective: To investigate the frequency, epidemiol- (50.6% vs 31.8%; PϽ.001). In patients with molluscum ogy, clinical features, and prognostic significance of in- dermatitis, numbers of MC lesions increased during the flamed molluscum contagiosum (MC) lesions, mollus- next 3 months in 23.4% of those treated with a topical cum dermatitis, reactive papular eruptions resembling corticosteroid and 33.3% of those not treated with a topi- Gianotti-Crosti syndrome, and atopic dermatitis in pa- cal corticosteroid, compared with 16.8% of patients with- tients with MC. out dermatitis. Patients with inflamed MC lesions were less likely to have an increased number of MC lesions Design: Retrospective medical chart review. over the next 3 months than patients without inflamed MC lesions or dermatitis (5.2% vs 18.4%; PϽ.03). The Setting: University-based pediatric dermatology practice. GCLRs were associated with inflamed MC lesion (PϽ.001), favored the elbows and knees, tended to be Patients: A total of 696 patients (mean age, 5.5 years) pruritic, and often heralded resolution of MC. Two pa- with molluscum. tients developed unilateral laterothoracic exanthem– like eruptions. Main Outcome Measures: Frequencies, characteristics, and associated features of inflammatory reactions Conclusions: Inflammatory reactions to MC, including to MC in patients with and without atopic dermatitis. the previously underrecognized GCLR, are common. Treat- ment of molluscum dermatitis can reduce spread of MC Results: Molluscum dermatitis, inflamed MC lesions, and via autoinoculation from scratching, whereas inflamed MC Gianotti-Crosti syndrome–like reactions (GCLRs) oc- lesions and GCLRs reflect cell-mediated immune re- curred in 270 (38.8%), 155 (22.3%), and 34 (4.9%) of sponses that may lead to viral clearance. the patients, respectively. A total of 259 patients (37.2%) had a history of atopic dermatitis. Individuals with atopic Arch Dermatol. 2012;148(11):1257-1264. dermatitis had higher numbers of MC lesions (PϽ.001) Published online August 20, 2012. and an increased likelihood of molluscum dermatitis doi:10.1001/archdermatol.2012.2414

OLLUSCUM CONTAGIO- a few months to years5; however, a variety sum (MC) is a self- of treatments have been used to speed its limited viral skin infec- clearance in patients with bothersome symp- tion that typically toms or cosmetic concerns. Up to 39% of presents as umbili- adults in the general population have anti- catedM papules and occurs most commonly bodies to the MC virus, suggesting a high in children. A recent population-based study rate of mild or subclinical infections.6 found that 20% of Japanese children devel- Several types of inflammatory reactions oped MC by 6 years of age.1 In surveys of can occur in association with MC. Lesions general practitioners in the Netherlands of MC may become inflamed and are often (1987 and 2001) and the United Kingdom surrounded by eczematous dermatitis (1994-2003), the cumulative incidence of (“molluscum dermatitis”).7-9 Gianotti- MC by 15 years of age was approximately Crosti syndrome–like reactions (GCLRs) 17%, with slightly higher incidence rates in have also been reported in a few patients Author Affiliations: The Ronald more recent years.2-4 Only 5% to 10% of MC with MC.10-13 Although inflammatory reac- Author Affil O. Perelman Department of O. Perelman Dermatology, New York cases in these studies occurred in individu- tions are well-recognized manifestations of Dermatology 2-4 University School of Medicine, als older than 14 years. In most affected MC infection, there are a paucity of pub- University Sc New York, New York. children, MC spontaneously resolves within lished data on their frequency, epidemiol- New York, N

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Patients, No. 40 Patients, No. 60 30 40 20 20 10 0 0 <1 1 2 3 4 5 6 7 8 9 10 11 12 ≥13 <1 1-3 4-6 7-12 13-18 19-24 25-36 >36 Age, y Duration, mo

Figure 1. Ages of patients at presentation. Figure 2. Duration of molluscum contagiosum prior to presentation in the 434 patients for whom these data were available. ogy, clinical spectrum, and prognostic significance. Fur- thermore, the effects of previous and concurrent atopic dermatitis (AD) on the incidence, spread, and response to RESULTS treatment of MC have varied in different studies.1,5,14-18 To better characterize the demographic and clinical PATIENT CHARACTERISTICS features of inflammatory responses to MC and the rela- tionship between AD and MC, we performed a retro- A total of 696 patients (336 boys, 360 girls) with MC were spective study of 696 patients with MC seen in our uni- identified. The mean age at presentation was 5.5 years (me- versity-based pediatric dermatology practice over a 5-year dian age, 5 years [range, 7 months to 17 years]) (Figure 1). period; MC-associated GCLR occurred in 34 patients, and Two children had immune disorders (IgA deficiency and its relevance to the course of the infection was noted. Data familial Mediterranean fever treated with colchicine). Five on the number, location, and duration of MC in pa- other patients were taking at least 1 systemic immunosup- tients with and without AD and inflammatory reactions pressive medication: prednisone (2 patients), mycophe- were collected. In addition, the treatments used for MC nolate mofetil (2 patients), cyclosporine, and 6-mercapto- and associated dermatitis were documented. purine. None of the patients were known to be infected with the human immune deficiency virus (HIV). METHODS A total of 307 (44.1%) had a history of atopy. This included 259 patients (37.2%) with AD and 138 patients (19.8%) with asthma or allergies (environmental or food). A retrospective review was performed of the medical charts of patients at the New York University Pediatric Dermatology Fac- Among patients with a history of AD, 169 (65.3%) had ac- ulty Practice who were diagnosed from January 1, 2005, through tive dermatitis: 53.9% only at sites of MC, 22.5% only at December 31, 2010, as having “molluscum contagiosum” ac- other sites, and 23.7% at both sites of MC and other sites. cording to the International Classification of Diseases, Ninth Re- A total of 293 patients (42.1%) had a family history of atopy vision, Clinical Modification. Data were gathered on these pa- (AD, asthma, or environmental allergies), and 179 patients’ demographics (age, sex), medical and family histories, tients (25.7%) had 1 or more household members with MC number and distribution of MC, presence of active AD and other (176 siblings, 2 parents, and 1 grandparent). Figure 2 de- inflammatory skin reactions, laboratory studies, treatment mo- picts the duration of MC prior to presentation in the 434 dalities, and MC course and duration. Qualitative estimates of patients for whom these data were available. the number of MC lesions were converted to quantitative ranges as follows: 5 or fewer lesions for “few”; 6 to 15 lesions for “mul- tiple”; 31 to 50 lesions for “many”; and more than 50 lesions LOCATION AND NUMBERS OF MC LESIONS for “numerous” or “innumerable” (there were no quantitative estimates for the 16-30 category). In less than 10 patients to The distribution of the patients’ MC lesions is presented whom cimetidine was administered and the number of MC le- in Table 1. Molluscum contagiosum lesions were lim- sions was not specified, it was estimated that there were 31 to ited to 1 region in 213 patients (30.6%), most often the 50 lesions, as it is our practice to give cimetidine only to pa- extremities (125 patients [18.0%]) or trunk (39 patients with more than 30 MC lesions. Time periods charted as tients [5.6%]). Molluscum contagiosum lesions were a “few” weeks or months were converted to 3 weeks or months, present on both the trunk and extremities in 302 patients respectively. (43.4%). Most patients’ peak number of MC lesions was Approval by the New York University Medical Center in- less than 50 (Figure 3). stitutional review board was obtained prior to beginning the medical chart review. There was no direct patient contact, and Several patterns of inflammation were associated with no identifiable patient data were recorded from the medical chart. having more than 50 MC lesions. Fifty-one of 259 pa- Statistical analysis was performed via calculation of descrip- tients (19.7%) with AD (whether or not it was active) had tive frequencies and use of 2-tailed ␹2 tests (using commer- more than 50 MC lesions vs 22 of 437 patients (5.0%) cially available software) for comparisons between groups. without AD (P Ͻ .001). Similarly, 46 of 270 patients

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No. of Patients (% of Individuals With Each Type of Lesion/Reaction) Molluscum Inflamed MC Lesions in Patients MC Lesions Dermatitis MC Lesions With a GCLR Body Site (n = 696 Patients) (n = 270 Patients) (n = 155 Patients) (n = 34 Patients) Trunk 379 (54.5) 79 (29.3) 53 (34.2) 21 (61.8) Extremities 542 (77.9) 186 (68.9) 83 (53.5) 24 (70.6) Face 123 (17.7) 17 (6.3) 6 (3.9) 1 (2.9) Scalp 4 (0.6) 0 0 0 Buttocks 153 (22.0) 27 (10.0) 19 (12.3) 10 (29.4) Groin 107 (15.4) 12 (4.4) 17 (11.0) 5 (14.7) Neck 97 (13.9) 14 (5.2) 6 (3.9) 4 (11.8) Axilla(e) 98 (14.1) 30 (11.1) 10 (6.5) 3 (8.8) Palms or soles 5 (0.7) 0 0 0

Abbreviation: GCLR, Gianotti-Crosti syndrome–like reaction.

(17.0%) with molluscum dermatitis had more than 50

MC lesions vs 27 of 426 patients (6.3%) without mol- All patients Ͻ 35 luscum dermatitis (P .001). In addition, 25 of 155 pa- Children with AD tients (16.1%) with inflamed MC lesions had more than 30 Children with history of AD 50 MC lesions vs 48 of 541 patients (8.8%) without inflamed MC lesions (P Ͻ .02). In contrast, patients with 25 a GCLR were not more likely than those without this type of reaction to have more than 50 MC lesions (3 of 34 20 Ͼ [8.8%] vs 70 of 662 [10.6%]; P .99). 15 Patients, % INFLAMED MC LESIONS 10

5 A total of 155 patients (22.3%) had at least 1 inflamed MC lesion, and 102 patients (14.7%) had at least 2 inflamed 0 ≤ ∗ MC lesions. Inflamed MC lesions were characterized by sub- 5 6-15 16-30 31-50 >50 stantial erythema and swelling, including pustular or fluc- Molluscum, No. tuant lesions. The locations of these lesions are shown in Table 1. A systemic antibiotic was administered to 24 chil- Figure 3. Number of molluscum contagiosum lesions in patients with and without atopic dermatitis (AD). *Statistically significant difference between dren with inflamed MC lesions owing to suspicion of in- the groups of patients without AD and with AD (whether or not it was active) fection (furunculosis [22 patients] or cellulitis [2 pa- for having more than 50 MC lesions (P Ͻ .001). tients]). A pathogenic organism (Staphylococcus aureus) was isolated in only 2 of 10 culture samples performed of pu- matitis associated with their MC lesions (50.6% vs 31.8%; rulent exudate from these lesions. Inflamed MC lesions were P Ͻ .001). The locations of molluscum dermatitis are equally common in patients with and without AD (57 of shown in Table 1. A total of 249 patients with mollus- 259 [22.0%] vs 98 of 437 [22.4%], P = .93). cum dermatitis (92.2%) were treated with a topical cor- Among the 58 patients who were seen in follow-up ticosteroid (primarily low to mid potency agents). Among within 3 months of presenting with inflamed MC le- the 146 patients with molluscum dermatitis who were sions, the overall number of MC lesions increased in 3 seen in follow-up within 3 months (Table 2), the num- patients (5.2%), remained the same in 12 patients (20.7%), ber of MC lesions increased in 32 of 137 patients (23.4%) and decreased in 43 patients (74.1%). On average, the who received topical corticosteroid therapy and 3 of 9 number of MC lesions decreased 65.0% in the latter group, patients (33.3%) who were not treated with a topical cor- and complete resolution occurred in 12.1% of these pa- ticosteroid (P = .44). Although a smaller proportion of tients. The number of MC lesions was less likely to in- patients without dermatitis (19 of 113 [16.8%]) had an crease over the subsequent 3 months in patients with in- increased number of MC lesions after 3 months of fol- flamed MC lesions (3 of 58 patients [5.2%]) than in those low-up compared with those with dermatitis (35 of 146 without inflamed MC lesions or dermatitis (16 of 87 pa- [24.0%]), the difference was not significant (P = .16). tients [18.4%]; P Ͻ .03) (Table 2). GIANOTTI-CROSTI MOLLUSCUM DERMATITIS SYNDROME–LIKE REACTIONS

Molluscum dermatitis (eczematous dermatitis surround- Thirty-four patients (12 girls and 22 boys) developed a ing MC lesions) was present in 270 patients (38.8%). Pa- GCLR during the course of their MC. The GCLRs were tients with a history of AD, when compared with those characterized by an eruption of numerous monomor- without a history of AD, were more likely to have der- phous, edematous, erythematous papules or papulo-

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©2012 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 Table 2. Change in Number of Molluscum Contagiosum (MC) Lesions in Patients Who Had Follow-up Visits Within 3 Months

Patients, No. (%) Decrease in the No. No Change in the No. Increase in the No. Type(s) of Associated Inflammation of MC Lesions of MC Lesions of MC Lesions Inflamed MC,n=58 43(74.1) 12 (20.7) 3 (5.2) Inflamed MC ϩ dermatitis,n=32 26(81.3) 6 (18.8) 0 Inflamed MC, no dermatitis,n=26 17(65.4) 6 (23.1) 3 (11.5) Molluscum dermatitis, n = 146 91 (62.3) 20 (13.7) 35 (24.0) Molluscum dermatitis with topical corticosteroid therapy, n = 137 85 (62.0) 20 (14.6) 32 (23.4) Molluscum dermatitis without topical corticosteroid therapy,n=9 6(66.7) 0 3 (33.3) No molluscum dermatitis or active atopic dermatitis, n = 113 74 (65.5) 20 (17.7) 19 (16.8) No inflamed MC, molluscum dermatitis, or active atopic dermatitis,n=87 57(65.5) 14 (16.1) 16 (18.4)

A B

Figure 4. Patients with Gianotti-Crosti syndrome–like reactions to molluscum contagiosum. Pruritic, edematous, pink papules on the elbow (A) and knees (B). Central crusts are evident in some lesions. Note the coalescence to form a plaque on the elbow and koebnerization secondary to scratching on the knee.

ated within the month prior to the onset of the GCLR in 13 patients (38.2%). The GCLR involved the extremities in 32 patients (94.1%), affecting the arms in 30 patients and legs in 29 patients. The eruption was bilateral in all patients. Twenty- three patients (67.6%) with a GCLR had exclusive involvement of the extensor aspects of the extremities, and lesions were limited to the knees and/or elbows in 12 patients (35.3%). Palmoplantar lesions occurred in only 1 patient. Other areas affected by the GCLR included the face (7 patients), trunk (5 patients), and buttocks (4 patients). Two patients (1- and 4-year-old boys) initially had involvement primarily on 1 side of the trunk that re- sembled a unilateral laterothoracic exanthem (ULTE). In 1 of these children, the MC lesions were limited to the Figure 5. Histologic findings of a Gianotti-Crosti syndrome–like reaction. same truncal region, and a more classic GCLR affecting A perivascular infiltrate composed of lymphocytes, histiocytes, and a few the extensor aspects of the extremities later developed. eosinophils is evident in the superficial and mid-dermis. Some lymphocytes The locations of MC lesions in patients with a GCLR extend into the overlying epidermis, where there is spongiosis, intraepidermal vesiculation, and focal scale crust. No molluscum bodies are (Table 1) were similar to those in the study population present, further differentiating this reaction pattern from inflamed molluscum overall. In patients with a GCLR, the number of MC le- lesions (hematoxylin-eosin, original magnification ϫ10). sions was 5 or fewer in 23.5%, 6 to 15 in 11.8%, 16 to 30 in 35.3%, 31 to 50 in 14.7%, and more than 50 in 8.8%. vesicles separate from MC lesions (Figure 4). The mean A GCLR was equally common in patients with and with- age of these patients was 5.6 years (median age, 5.5 years out AD (13 of 259 [5.0%] vs 21 of 437 [4.8%]; P Ͼ .99). [range, 11 months to 12 years]). Pruritus was a promi- A biopsy was performed of the GCLR in 1 patient. His- nent feature of the GCLR in 27 patients (79.4%). The erup- tologic evaluation showed a superficial and mid-dermal tion was present at the initial visit in 17 patients (50.0%), perivascular infiltrate composed of lymphocytes, histio- and in the others it developed a mean of 1.7 months af- cytes, and scattered eosinophils (Figure 5). Some ter their first visit. Treatment of the MC had been initi- lymphocytes extended into the overlying epidermis. Spon-

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450

400

350

300

250

Patients Treated, No. Patients Treated, 200

150

100

0 Cantharidin Imiquimod Cimetidine Curettage Retinoid Homeopathy Cryotherapy Fluorouracil Podofilox Cream, 5% Treatments Administered

Figure 6. Treatments administered. Retinoid refers to topical use of a retinoid cream.

giosis, intraepidermal vesiculation, and focal scale- plied in 475 patients (a mean of 1.9 treatment sessions per crust were evident. patient [range, 1-10]; treated areas were washed with soap The mean duration of the GCLR was 6 weeks in the and water 2 to 3 hours after application), and curettage was 13 patients for whom this information was available. The used in 100 patients (a mean of 1.4 treatment sessions per eruption lasted less than 1 month in 5 of these patients patient [range, 1-5 sessions]). A second agent was later and a mean of 2 months in the other 8 patients. The GCLR added in some patients who were treated initially with can- was typically treated with a topical corticosteroid of mid- tharidin or curettage, including imiquimod cream in 35 pa- potency or higher and usually responded with substan- tients, a topical retinoid in 17 patients, and oral cimeti- tial improvement within 1 week. The mean time be- dine (approximately 40 mg/kg daily divided into 2 doses, tween onset of the GCLR and resolution of the MC lesions a maximum of 1600 mg daily) in 111 patients. None of the was 2 months (median, 5 weeks [range, Ͻ1-8 months]) patients experienced a serious adverse effect related to any in the 12 patients for whom these data were available. of the treatments administered. In the 42 patients (treated In addition, a substantial (50%-95%) reduction in the with various modalities) for whom data on the timing of number of MC lesions occurred in all 9 patients with a both the onset and resolution of the MC were available, the GCLR who were followed for at least 2 months after its MC lesions were present for a mean of 8.0 months (me- onset, but they were lost to follow-up prior to complete dian, 6.6 months [range, 1.5-29.0 months). resolution of the MC lesions. COMMENT RELATIONSHIPS AMONG DIFFERENT TYPES OF INFLAMMATORY REACTIONS This study further characterizes both classic and more Inflamed MC lesions were observed in 22 of 34 patients recently recognized types of inflammatory reactions as- (64.7%) with a GCLR, compared with only 133 of 662 sociated with MC. Data from other large series of pedi- patients (20.1%) without a GCLR (P Ͻ .001). In con- atric patients with MC that described the frequencies of trast, patients with and without a GCLR were equally likely inflamed MC lesions, molluscum dermatitis, and AD are to have molluscum dermatitis (12 of 34 [35.3%] vs 258 summarized in Table 3.1,5,14,15,17,19-22 of 662 [39.0%]; P = .67). Similar proportions of patients Inflamed MC lesions typically present as erythema- with and without molluscum dermatitis had inflamed mol- tous, edematous papules and papulonodules that may be- luscum (70 of 270 [25.9%] vs 85 of 426 [20.0%]; P = .08). come pustular or fluctuant. In this study and the 2 previous large MC series that provided data on this reaction TREATMENT AND COURSE pattern (Table 3), 20.8% of patients overall (343 of 1646) Data on the treatments administered are presented in were noted to have inflamed MC lesions.15,17 Despite their Figure 6. Cantharidin (0.7% in a collodion base) was ap- furuncle-like appearance, the results of the current study

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©2012 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 Table 3. Data on the Prevalences of Atopic Dermatitis (AD) and Inflammatory Reactions in Patients With Molluscum Contagiosum (MC)a

Patients Molluscum Inflamed AD, % of Patients With MC, Dermatitis, MC Lesions, Source No. Ages (Mean), y By History Active % of Patients % of Patients Present study 696 0.6-17 (5.5) 37 24 39 22 Osio et al,15 2011 650 0.5-15 (6) 43 25 19 21 Seize et al,19 2011 113 1-15 (5.5) 34 22 47 12 Hayashida et al,1 2010 180 1-6 (3.6) 21 NA NA NA Dohil et al,14 2006 302 Յ5 in 53% and Յ8 in 80% of patients 24 24 NA NA Kakourou et al,20 2005 110 0.5-11 (4.8) 18 NA NA NA Laxmisha et al,21 2003 137 0.5-14 (6.2) NA NA 9 1 Agromayor et al,5 2002 107 1-14 (6) 45 NA NA NA Silverberg et al,17 2000 300 NA (4.7) 41 NA 20 17 Choong and Roberts,22 1999 198 0.5-47 (7.8) 32 NA NA NA

Abbreviation: NA, data not available. a Limited to series of at least 100 patients with MC.

confirm that the purulent exudate from inflamed MC le- for these noneczematous reactions. Patients with mol- sions is usually sterile. However, superinfections with S luscum dermatitis were more likely to have a large num- aureus occasionally occur, and antibiotic administra- ber of MC lesions, likely related at least in part to spread tion (as well as drainage when appropriate) should be of MC lesions by scratching due to increased pruritus. considered when there is lymphangitic streaking or spread There is evidence that MC is more common in chil- of erythema suggestive of cellulitis. dren with AD than in those without AD. The prevalence Inflammation usually leads to regression of affected rates of AD in this study and other pediatric MC series MC lesions and sometimes heralds clearance of the en- based in the United States, South America, Europe, Aus- tire eruption, including lesions that do not develop clini- tralia, and Japan have ranged from 18% to 45% (Table 3), cally evident inflammation.23 In this study, patients with an overall mean of 36% (944 of 2656).1,5,14,15,17,19,20,22 with inflamed MC lesions were significantly less likely These rates are higher than the estimated AD preva- to have an increased number of MC lesions during the lence of approximately 10% to 20% in pediatric popula- next few months than those without inflamed MC le- tions.25-27 However, MC-infected children with a history sions. Cell-mediated immunity presumably plays a role of AD may be more likely to see a physician for skin prob- in the clearance of MC, explaining the increased likeli- lems, which could potentially affect the results of MC se- hood of widespread, severe and persistent MC in pa- ries based on medical records.14 A 2010 population- tients with HIV infection.24 Histologically, inflamed MC based study of nursery school children in Japan found a lesions demonstrate a dense, mixed inflammatory infil- 1.6-fold increased likelihood of MC (95% CI, 1.00- trate (eg, lymphocytes, histiocytes, and neutrophils).23 2.68) in children with AD.1 In the current series, chil- In the current study, the presence of inflamed MC le- dren with a history of AD were more likely to have a large sions was associated with the development of a GCLR, number of MC lesions than those without AD. Like- which can also be a harbinger of MC clearance and likely wise, in a recent study of curettage treatment for MC, pa- also has a cell-mediated immune basis but not mollus- tients with AD had more lesions and more frequent re- cum dermatitis. Unfortunately, the limited follow-up data lapses than those without AD.16 In contrast, a history of AD in this retrospective study and previous series have pre- was not associated with the number of MC lesions or re- cluded a more thorough analysis of the duration of MC currence of MC in a recent large French series.15 In the in patients with and without inflamed lesions, espe- current study, a history of AD was associated with hav- cially considering that patients whose MC lesions re- ing dermatitis surrounding MC lesions (as discussed solve are unlikely to return for follow-up visits. in this section) but not with the development of in- Molluscum dermatitis presents as a pruritic eczema- flamed MC lesions or a GCLR. tous eruption in the skin surrounding MC lesions. The Gianotti-Crosti syndrome (papular acrodermatitis dermatitis can be diffuse or nummular and may be more of childhood) is an exanthem that can be triggered by prominent than the MC lesions themselves, with MC le- infections with a wide variety of viruses, including Epstein- sions obscured by dermatitic patches and plaques.8,9 Mol- Barr virus (EBV) and hepatitis B virus. It presents as a luscum dermatitis was evident in 38.8% of the patients symmetric eruption of monomorphous, edematous, ery- in this study and in 9% to 47% of those in previous MC thematous papules, or papulovesicles that favor the exten- series, with an overall mean incidence of 27% (505 sor surfaces of the extremities, buttocks, and cheeks. To our of 1896; Table 3).15,17,19,21 Like the study by Osio et al,15 knowledge, prior to the 34 cases described herein, only 2 the current study found that molluscum dermatitis is more cases of patients (5- and 8-year-old children) with a GCLR likely to develop in children with a history of AD, affect- associated with MC have been reported.10,11 One of these ing most (50.6%) patients in this subgroup. However, an children had negative results from serologic testing for mul- association between molluscum dermatitis and the de- tiple viruses (including EBV and hepatitis B virus),11 and velopment of inflamed MC lesions or a GCLR was not the other had coexistent molluscum dermatitis and was observed, suggesting different inflammatory pathways diagnosed as having an “id reaction.”10 The morphologic

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©2012 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 characteristics, distribution, and pruritus of GCLRs in the time frame. These results suggest that the eczematous der- setting of MC are indeed reminiscent of id reactions (eg, matitis itself, rather than immunomodulatory effects of the disseminated eczema associated with allergic contact der- corticosteroid used to treat it, was responsible for the de- matitis or a dermatophyte infection). Compared with clas- velopment of new MC lesions. The association between sic Gianotti-Crosti syndrome, GCLRs triggered by MC tend topical corticosteroid use and recurrence of MC ob- to exhibit more prominent pruritus, a relatively localized served by Osio et al15 may be explained by autoinocula- distribution (eg, limited to the elbows and knees), and a bet- tion of MC virus related to pruritus and resultant scratch- ter response to topical corticosteroid therapy. The histo- ing of the dermatitis that was being treated. Using a topical logic findings in the patient described herein whose GCLR corticosteroid could also make MC lesions previously ob- was biopsied and 1 previously reported patient included epi- scured by dermatitis become visible, providing another dermal spongiosis and a dermal perivascular lymphohis- possible explanation for an apparent “recurrence” of MC. tiocytic infiltrate, which would be compatible with either Observations in the current study and experiences of other Gianotti-Crosti syndrome or an id reaction.11 pediatric dermatologists suggest that control of surround- The observation of GCLRs in 5% of the patients with MC ing dermatitis may help to prevent the spread of MC that in the current series suggests that this inflammatory re- often occurs secondary to scratching.29,30 sponse to MC is more common than suggested by the pau- In series of children with MC, the proportion of pa- city of previous reports. The association of GCLRs with MC tients with known immune disorders (eg, HIV infection, may be underrecognized when the MC lesions are few primary immunodeficiencies) or taking a systemic immu- in number, in “hidden” sites (eg, the axillae or groin), nosuppressive medication has been extremely low. For ex- masked by inflammation, or obscured by dermatitis. Be- ample, only 7 of the 696 patients (1.0%; none with HIV cause the papules or papulovesicles of a GCLR can re- infection) in this series and none of the 661 pediatric pa- semble MC lesions, a GCLR may even be mistaken (espe- tients with MC in the largest previous study were immu- cially by parents) for a sudden increase in the number nocompromised.15 At a tertiary care center, patients of (inflamed) molluscum. Dermoscopy can help to iden- with complicated medical histories (including immune dis- tify MC lesions, which are characterized by a multilobu- orders and receipt of immunomodulatory therapy) would lated, white to yellow, amorphous central structure sur- likely account for a larger proportion of patients with MC rounded by a “crown” of blood vessels.28 than in the general community. In a 5-year population- Molluscum-associated GCLRs tend to be relatively short- based study of Native Americans and Alaskan Natives, only lived, lasting a mean of 6 weeks in the patients in this study 13 of 13 700 visits (Ͻ0.1%) for MC over a 5-year period who returned for follow-up visits and 3 or fewer weeks (fol- involved patients with HIV infection.31 lowing removal of MC lesions via curettage) in the 2 pre- There is no gold standard for the treatment of MC, vious reports. The development of a GCLR in a patient as reflected in the variety of destructive and immuno- with MC seems to be a good prognostic sign. All of the pa- modulatory methods that are used.29,30,32 Although watch- tients with GCLR for whom follow-up data were available ful waiting is often appropriate given the self-limited na- experienced a dramatic reduction in the number of MC le- ture of MC, treatment can help to alleviate pruritus and sions, with complete clearance of the MC lesions occur- discomfort, prevent spread via autoinoculation or trans- ring a median of 5 weeks after onset of the GCLR. mission to other children, and eliminate the social stigma Two patients in this series had a reactive papular erup- of visible lesions.29,30,32 In a recent survey of members of the tion that initially involved 1 axilla and the ipsilateral trunk, Society for Pediatric Dermatology,32 the most common resembling an ULTE. Like Gianotti-Crosti syndrome, therapeutic methods used for MC were cantharidin, imi- ULTE is thought to have a viral trigger, but no etiologic quimod, and curettage (used by 95%, 85%, and 72% of re- agent has been consistently demonstrated. Affected chil- spondents, respectively). Each of these modalities was dren present with a morbilliform or eczematous erup- frequently used in the current study (Figure 6), which tion that initially involves 1 axilla and the adjacent trunk represents the largest published experience with can- and/or upper arm, eventually becoming bilateral. There tharidin (475 patients) to date. This and other series, such have been 2 previous reports12,13 of a predominantly uni- as the report of cantharidin therapy in 300 patients lateral truncal exanthem lasting 1 to 2 months in chil- with MC by Silverberg et al in 2000,17 provide support dren with MC in the same distribution and negative re- for its safety and efficacy. sults from serologic studies for other viruses. In the current The tendency for spontaneous resolution of MC makes study, the MC lesions resolved within 2 weeks of onset it difficult to determine the effectiveness of treatment of the ULTE-like eruption in the patient with this reac- in retrospective series and uncontrolled studies. One pro- tion who returned for follow-up. spective randomized study found that curettage (follow- Osio et al15 noted that use of topical corticosteroids ing use of a topical anesthetic with or without systemic within the previous 3 months was associated with a higher sedation) required fewer patient visits for elimination risk of recurrence following treatment of MC. Among pa- of MC and had a lower rate of adverse effects than topi- tients in the current study with molluscum dermatitis, cal application of cantharidin or imiquimod.33 Random- the number of MC lesions increased during the follow- ized studies have also shown that imiquimod therapy ing 3 months in 23.4% of those who were treated with a for MC has efficacy similar to that of cryotherapy or topi- topical corticosteroid and in 33.3% of those who were cal application of potassium hydroxide.34,35 Although cryo- not treated with a topical corticosteroid (Table 2). A therapy (when performed weekly) may result in more smaller proportion (16.8%) of patients without derma- rapid clearance of MC lesions than imiquimod (eg, 3-6 titis had an increased number of MC lesions during this weeks vs 6-12 weeks), the former modality produces more

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©2012 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 discomfort and pigmentary sequelae.34 Additional pro- 11. Carrascosa JM, Just M, Ribera M, Ferra´ndiz C. Papular acrodermatitis of child- spective controlled studies are needed to evaluate the ben- hood related to poxvirus and parvovirus B19 infection. Cutis. 1998;61(5):265- 267. efits and patient tolerance of different treatments for MC. 12. Mo¨hrenschlager M, Ring J, Lauener R. A boy with a one-sided red rash. Eur In conclusion, this series documents the frequencies J Pediatr. 2011;170(4):539-540. and clinical presentations of inflammatory reactions 13. Baek YS, Oh CH, Song HJ, Son SB. Asymmetrical periflexural exanthem of child- to MC, highlighting their relationships with one an- hood with concurrence of molluscum contagiosum infection. Clin Exp Dermatol. other, AD, and the course of the MC infection. The in- 2011;36(6):676-677. 14. Dohil MA, Lin P, Lee J, Lucky AW, Paller AS, Eichenfield LF. The epidemiology cidence, features, and prognostic implications of the re- of molluscum contagiosum in children. J Am Acad Dermatol. 2006;54(1): cently recognized GCLR in patients with MC are 47-54. characterized for the first time. Better understanding of the 15. Osio A, Deslandes E, Saada V, Morel P, Guibal F. Clinical characteristics of mol- pathogenesis of these inflammatory reactions and their luscum contagiosum in children in a private dermatology practice in the greater effects on the natural history of MC may help to de- Paris area, France: a prospective study in 661 patients. Dermatology. 2011; velop more effective treatment options for this common 222(4):314-320. 16. Simonart T, De Maertelaer V. Curettage treatment for molluscum contagiosum: childhood infection. a follow-up survey study. Br J Dermatol. 2008;159(5):1144-1147. 17. Silverberg NB, Sidbury R, Mancini AJ. Childhood molluscum contagiosum: ex- Accepted for Publication: May 25, 2012. perience with cantharidin therapy in 300 patients. J Am Acad Dermatol. 2000; Published Online: August 20, 2012. doi:10.1001 43(3):503-507. /archdermatol.2012.2414 18. Braue A, Ross G, Varigos G, Kelly H. Epidemiology and impact of childhood molluscum contagiosum: a case series and critical review of the literature. Pediatr Correspondence: Julie V. Schaffer, MD, The Ronald O. Dermatol. 2005;22(4):287-294. Perelman Department of Dermatology, New York Uni- 19. Seize MB, Ianhez M, Cestari SdaC. A study of the correlation between mollus- versity School of Medicine, 240 E 38th St, 11th Floor, cum contagiosum and atopic dermatitis in children. An Bras Dermatol. 2011; New York, NY 10016 ([email protected]). 86(4):663-668. Author Contributions: All authors had full access to all 20. 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