Journal Pre-proof

Blistering exanthems in the times of monkeypox- keep calm and do not panic!

Nikhil Mehta, MD, Somesh Gupta, MD

PII: S0190-9622(22)03317-5
DOI: https://doi.org/10.1016/j.jaad.2022.12.026
Reference: YMJD 17357

To appear in: Journal of the American Academy of Dermatology

Received Date: 4 October 2022

Revised Date: 9 December 2022
Accepted Date: 9 December 2022

Please cite this article as: Mehta N, Gupta S, Blistering exanthems in the times of monkeypox-
keep calm and do not panic!, Journal of the American Academy of Dermatology (2023), doi: https://
doi.org/10.1016/j.jaad.2022.12.026.

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition
of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of
record. This version will undergo additional copyediting, typesetting and review before it is published
in its final form, but we are providing this version to give early visibility of the article. Please note that,
during the production process, errors may be discovered which could affect the content, and all legal
disclaimers that apply to the journal pertain.

© 2022 Published by Elsevier on behalf of the American Academy of Dermatology, Inc.

Page No. 1

Article type: Letter to Editor

Title: Blistering exanthems in the times of monkeypox- keep calm and do not panic!

Authors: Nikhil Mehta, MD; Somesh Gupta, MD

Department of Dermatology and Venereology, All India Institute of Medical Sciences,

New Delhi, India

Corresponding Author:

Dr Somesh Gupta, MD, Professor, Department of Dermatology and Venereology

All India Institute of Medical Sciences, 110029, New Delhi, India

f
oo
Email id: someshgupta@aiims.edu, Ph: 91-11-2659-3217

r
Acknowledgements: We thank our patients and their attendants for giving consent for the
publication of their photographs
-p
re
Author contribution: all authors contributed equally to the manuscript
lP

Conflict of interest: none, no potential conflicts of interest exist for any co-author
na

Patients consent for publication of identifiable photos: Consent for publication of

photographs has been obtained from the patients/attendants. No pictures show any patients’
ur

identifiable face/feature.
Jo

Funding sources: none

Institute review board/ethics committee approval: not required

Prior publication/presentation: none

Reprint requests: Nikhil Mehta

Manuscript word count: 495 words (excluding references, tables and figures)

References: 5

Figures: 0

Supplementary file: 2 Supplementary Figures (http://dx.doi.org/10.17632/jzj496vbf2.2)

Tables: 2
Page No. 2

Keywords: Monkeypox, Chickenpox, Hand Foot and Mouth disease, papular acrodermatitis,
Gianotti-Crosti syndrome

f
r oo
-p
re
lP
na
ur
Jo
 Page No. 3

1 Manuscript

2 In the current outbreak of monkeypox, infectious disease specialists and dermatologists are

3 flooded with numerous consults every day, asking- “could this be monkeypox?” While

4 eruptive rashes of viral maculopapular exanthems, vasculitis, and erythema multiforme can

5 be usually differentiated, chickenpox and two other entities with seasonal, sporadic, and

6 periodic outbreak clusters in schools, families, or localities- hand, foot, and mouth disease

7 (HFMD) and papular acrodermatitis/Gianotti-Crosti syndrome (GCS) are at times difficult to

f
8 differentiate from monkeypox. Chickenpox and HFMD can be infrequently seen in adults in

oo
9 some parts of the world and have a high secondary attack rate, but warrant isolation for about

r
10 -p
1 week rather than 3 weeks for the slowly progressive monkeypox. This brief review will

11 compare the cutaneous (Table 1) and systemic (Table 2) manifestations of these potential
re
12 mimickers to help clinicians in their assessment and to allay the fears of patients and other
lP

13 healthcare staff.
na

14 Monkeypox lesions evolve through various morphologies, from a macule to a papule, then a
ur

15 vesicle, followed by a pustule, ulcer, and then scabbing slowly over 2-4 weeks; although at a
Jo

16 single point in time a patient has monomorphic lesions in the same phase of evolution.

17 Vesicles and resultant ulcers in monkeypox are deep-seated, especially at the palms and

18 soles. They are commonly distributed at oral, anal, and anogenital regions (‘bipolar’

19 distribution), along with acrofacial sites, and occasionally trunk.1-3 Lymphadenopathy,

20 especially inguinal, is another striking feature.1–4 Atypical features like lesions predominantly

21 at the trunk or face, few lesions, and simultaneous multiple morphologies are also seen in the

22 current outbreak in a minority of patients.2-4 Monkeypox lesions, along with chickenpox and

23 HFMD lesions, can also be hemorrhagic, pustular, centrally crusted, targetoid and

24 umbilicated, and these blistering exanthems cannot be reliably differentiated based on these

25 morphologies (Supplementary figure 1, accessible from

 Page No. 4

26 http://dx.doi.org/10.17632/jzj496vbf2.2). In settings where molecular testing for causative

27 viruses is not available, clinical differentiators remain paramount. Chickenpox occurs in non-

28 immunized individuals and has a centripetal distribution of polymorphous lesions in different

29 stages of evolution with superficial blisters lesions in crops. Rapid resolution (5-10 days) of

30 rash favors chickenpox compared to monkeypox. HFMD and GCS can have vesicles and

31 papulo-vesicles at acrofacial sites which can be umbilicated. However, HFMD has small

32 superficial blisters and rapidly-healing ulcers with background erythema at palms, soles, oral

33 cavity, and buttocks without any lymphadenopathy, usually in children less than 5 years old.5

f
oo
34 Similarly, GCS is characterized by papulo-vesicles on buttocks, extensors, and face lasting

r
35 for weeks in children are indicative of GCS.
-p
re
36 Differentials also include other genital diseases. Molluscum contagiosum has umbilicated
lP

37 lesions but solid papules instead of vesicles. Anogenital herpes has anogenital blisters but

38 they have characteristic polycyclic margins and are limited in area. Ulcer of primary
na

39 syphilitic chancre is painless, elevated, and indurated. Papules, papulo-vesicles, and

ur

40 excoriations of scabies and insect-bite hypersensitivity lack frank vesicles and pustules
Jo

41 (Supplementary figure 2, accessible from http://dx.doi.org/10.17632/jzj496vbf2.2).

42 In conclusion, despite some similarities, monkeypox can be differentiated from its mimickers

43 using the above-mentioned features which can be elicited with astute detailed history and

44 examination.

45
 Page No. 5

46 Tables

47 Table 1. Differentiation between monkeypox, chickenpox, hand foot and mouth disease
48 (HFMD) and Gianotti-Crosti syndrome (GCS)- cutaneous features

Disease Monkeypox Chickenpox HFMD GCS

• Centripetal • Acral (hands and • Extensors (thighs

Distribution • Centrifugal (trunk and feet, especially and buttocks,
(face, hands and proximal palms and soles) upper arms)
feet) extremities) • Oral cavity • Face
• Bipolar (oral • Face Extensors (knees,
cavity and • Infrequently elbows, buttocks)
anogenital area) at distal acral • Rarely genitals

f
areas and oral

oo
cavity
• Erythematous • Initially • Papules and
Morphology • Evolution from rash which erythematous papulo-vesicles

r
macules, quickly macules which which can be
papules,
vesicles,
-p
evolves into
superficial
rapidly
forming
evolve
small
crusted
eroded
and

•
re
pustules, and blisters with blisters and Rarely purpura
then scabbing surrounding superficial
• All lesions in erythema erosions
lP

same stage- (‘dew drop on surrounded by

monomorphic rose petal’) erythema
lesions • Lesions in
na

• Deep-seated multiple
well- crops-
circumscribed polymorphic
ur

blisters
• Septate
morphology
Jo

(divisions
within lesions)
may be seen on
opening lesions
• Anal pain,
bleeding and
ocular mucosal
involvement
also seen in
current outbreak
• 5-10 days
Duration of • 14-28 days from • 7-10 days • 2-8 weeks,
rash the onset till can last up to
scabbing 6 months
•

Sequelae Heal with Some deeper Resolves without Resolves without

scarring ulcers heal scarring scarring
with scarring

49
 Page No. 6

50 Table 2. Differentiation between monkeypox, chickenpox, hand foot and mouth disease
51 (HFMD) and Gianotti-Crosti syndrome (GCS)- systemic features

Disease Monkeypox Chickenpox HFMD GCS

• Children and • Children less • Children less
Population • Travellers to adults who did than 5 years than 12
affected not get it in old years old
countries childhood • Family
within the last • In countries with members of
21 days universal and adults
• History of varicella with history
contact with vaccination of contact
people with programs, with affected
similar rash or unvaccinated children
confirmed/pro children and • Infrequently

f
oo
bable adults older
monkeypox children and
• Groups adults
predisposed to without any

r
contact
•
STIs
Contact with
African
-p history
re
endemic
dead/live wild
lP

animal/pet

Fever 1-3 days before Fever with each new Mild fever 1-3 Infrequent mild fever
onset of rash, crop of blisters days before the may precede by
na

resolves when rash onset of rash, variable duration or

occurs resolves when accompany
rash occurs
ur

Lymphadenopath Common, cervical Rare Rare Common

Jo

y and inguinal

Other systemic Headache, malaise, Headache, myalgias, Infrequent upper Rare hepato-
features myalgias, sore nausea respiratory splenomegaly
throat, ocular symptoms
symptoms
• Secondary • Rarely • Rare cases
Complications • Secondary pyodermas dehydration, associated with
pyodermas • Infrequently can respiratory acute viral
• Infrequently cause and hepatitis can
can cause dehydration, neurological have long-term
dehydration, respiratory and involvement sequelae of
respiratory and neurological • Palmoplantar hepatitis
neurological involvement exfoliation
involvement which is more and
common in onychomade
adults and sis
immunocompro • Very low
mised patients mortality
52
 Page No. 7

53 References

54 1. Rodriguez-Morales AJ. Monkeypox and the importance of cutaneous manifestations for

55 disease suspicion. Microbes, Infection and Chemotherapy. 2022 Jun 6;2:e1450-.

56 https://doi.org/10.54034/mic.e1450

57 2. Tarín-Vicente EJ, Alemany A, Agud-Dios M, et al. Clinical presentation and virological

58 assessment of confirmed human monkeypox virus cases in Spain: a prospective observational

59 cohort study. Lancet. 2022;400(10353):661-669. doi:10.1016/S0140-6736(22)01436-2

f
oo
60 3. Pérez-Martín ÓG, Hernández-Aceituno A, Dorta-Espiñeira MM, García-Hernández L,

r
61 -p
Larumbe-Zabala E. Atypical presentation of sexually-transmitted monkeypox lesions. Infect

62 Dis (Lond). 2022 Dec;54(12):940-943. doi: 10.1080/23744235.2022.2121420. Epub 2022

re
63 Sep 14.
lP

64 4. Sharma A, Dudani P, Gupta S. Patterns of sexual transmission of monkeypox in the current

na

65 outbreak: An international survey of physicians [published online ahead of print, 2022 Nov
ur

66 15]. J Eur Acad Dermatol Venereol. 2022;10.1111/jdv.18745. doi:10.1111/jdv.18745

Jo

67 5. Sharma A, Mahajan VK, Mehta KS, Chauhan PS, Manvi S, Chauhan A. Hand, Foot and

68 Mouth Disease: A Single Centre Retrospective Study of 403 New Cases and Brief Review of

69 Relevant Indian Literature to Understand Clinical, Epidemiological, and Virological

70 Attributes of a Long-Lasting Indian Epidemic. Indian Dermatology Online Journal: May–Jun

71 2022 - Volume 13 - Issue 3 - p 310-320 doi: 10.4103/idoj.idoj_701_21

72

73