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CUTANEOUS MANIFESTATIONS AND ISSUES

RELATED TO DERMATOLOGIC CARE

INTRODUCTION

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory


syndrome coronavirus 2 (SARS-CoV-2), raises many critical issues in
dermatology and dermatologic care. Addressing these issues is necessary, yet
also challenging, because there are few direct data on which to base
recommendations [1].

This topic will discuss issues related to dermatologic care during the COVID-19
pandemic.

CUTANEOUS MANIFESTATIONS OF COVID-19

Case series from around the world have identified a range of potential
dermatologic manifestations of COVID-19 [2,3]. The frequency (ranging from
0.2 to 20.4 percent of cases) and timing of cutaneous manifestations of COVID-
19 are difficult to ascertain [4-6]. Also unclear is the association of certain skin
manifestations with the illness severity [7]. Moreover, it cannot be excluded that
in some patients the observed skin findings may represent cutaneous reactions
to the numerous treatments used for COVID-19 [7,8].

The American Academy of Dermatology's COVID-19 Registry, a collaboration


between the American Academy of Dermatology and the International League
of Dermatologic Societies, is attempting to collate cases and better define the
cutaneous manifestations of COVID-19 [9]. (See 'Registries'below.)

Reported dermatologic manifestations of COVID-19 include:

●Exanthematous (morbilliform) rash – In several case series, a


morbilliform rash predominantly involving the trunk has been reported as
the most common cutaneous manifestation of COVID-19 [2,3,5,10,11]. The
rash has been noted either at the disease onset or, more frequently, after
hospital discharge or recovery [5].
●Pernio (chilblain)-like acral lesions – Pernio (chilblain)-like lesions of
acral surfaces ("COVID toes") have been described across the age
spectrum in patients with confirmed or suspected COVID-19, in the
absence of cold exposure or underlying conditions associated with pernio
[2,3,12-17]. Our understanding of the pathogenesis of these lesions is still
under evolution, though it appears to be a primarily inflammatory process
[3,15,17,18]. They present as erythematous-violaceous or purpuric
macules on fingers, elbows, toes, and lateral aspect of the feet, with or
without accompanying edema and pruritus (picture 1). Resolution may
occur in two to eight weeks.
Patients presenting with new-onset, pernio-like lesions that have no other
clear cause should be tested for severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) by polymerase chain reaction (PCR). For
patients that have had these lesions for >4 weeks, immunoglobulin M (IgM)
and immunoglobulin G (IgG) antibody testing may be appropriate, following
local guidelines and depending on the quality of available tests. Work-up of
other causes of pernio is discussed in greater detail separately.
(See "Pernio (chilblains)".)
There are no treatment guidelines for COVID-19-associated, pernio-like
lesions of the feet or hands. However, high-potency topical corticosteroids
may be helpful if the lesions are causing discomfort.
●Livedo-like/retiform purpura/necrotic vascular lesions – Livedo
reticularis, retiform purpura, and livedoid lesions have been reported in
patients with COVID-19 [13,19-22]. Retiform purpura and necrotic vascular
lesions have been described in three patients with severe pulmonary
disease [21]. Histologic and immunohistochemistry studies of skin biopsies
revealed a pattern of complement-mediated microvascular injury in both
involved and normally appearing skin. Histopathologic findings of
thrombotic vasculopathy and/or laboratory coagulation alterations have
been demonstrated in patients with severe COVID-19 and acral, ischemic
lesions [18,22]. (See "Approach to the patient with retiform (angulated)
purpura" and "Livedoid vasculopathy"and "Coronavirus disease 2019
(COVID-19): Hypercoagulability".)
●Urticaria – Acute urticaria with or without concomitant fever has been
reported as a presenting sign of COVID-19 infection [2,3,5,13,23].
●Vesicular (varicella-like) eruptions – There are several reports
describing a vesicular-pustular, varicella-like eruption associated with
COVID-19 [2,13,24,25]. In a series of 24 patients, an eruption of small
papules, vesicles, and pustules appeared 4 to 30 days after the onset of
COVID symptoms and resolved in a median of 10 days [26]. A real-time
PCR for SARS-CoV-2 from vesicle content performed in four patients
yielded negative results. Seventeen of 24 patients were not taking any
medications, ruling out a drug reaction.
●Multisystem inflammatory syndrome in children (MIS-C) – An
erythematous, polymorphic rash, erythema and/or firm induration of hands
and feet, oral mucositis, and conjunctivitis, along with systemic, laboratory,
and imaging findings of atypical, severe Kawasaki disease, have been
described in a cohort of 10 Italian children during the COVID-19 pandemic
[27]. Similar cases have been reported in the United Kingdom [28], the
United States, and other countries. Case definitions for MIS-C have been
proposed by the World Health Organization and the United States Centers
for Disease Control and Prevention. (See "Coronavirus disease 2019
(COVID-19): Multisystem inflammatory syndrome in children".)

Less frequently reported dermatologic manifestations include papulosquamous


eruptions [29], erythema multiforme-like lesions [30-32], dengue-like rashes
[33,34], petechiae [35], and gangrene [36].

Some infants born to mothers with COVID-19 at birth have had transient rash.
In a review of nine small case series from China that included a total of 65
pregnant women who were infected with SARS-CoV-2 during pregnancy and 67
newborns, two newborns presented with a rash [37]. The rash has been
described in one infant as a diffuse, maculopapular eruption that resolved in
one day with desquamation and in another as a diffuse, red, miliaria-like
eruption that disappeared in 10 days without treatment [38].

DERMATOLOGIC CONDITIONS RELATED TO COVID-19

PANDEMIC Skin injury, mechanical/friction dermatitis, and irritant

contact dermatitis due to personal protective equipment (PPE) and hand


hygiene measures have been reported in the majority of health care workers
involved in the direct care of patients with COVID-19 [39].

Personal protective equipment-induced skin injury — Health care workers


caring for COVID-19 patients or patients potentially infected with severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) may spend long hours
wearing PPE. The American Academy of Dermatology has
released recommendations on preventing and treating occupationally induced
dermatologic conditions during the COVID-19 pandemic.

PPE-induced skin injury is common, occurring in 43 to 97 percent of Chinese


health care workers [39-41]. Long durations of PPE use (>6 hours per day)
increase rates of skin damage [39,40]. Masks, goggles, face shields, and gloves
apply pressure, create abrasion, and retain moisture and can injure the nasal
bridge, cheek, forehead, and hands [39-41].

PPE-induced injuries include desquamation, erythema, maceration, fissuring,


papules, and erosions, leading to itching and pain [40]. PPE use can also
aggravate underlying skin conditions [42].

Prevention of PPE-related injuries has the potential to reduce PPE protocol


breaches due to inadvertent adjustment and touching [43]. The use of barrier
films or dressings at pressure points before donning PPE may reduce these
types of injuries [42,44-47]. However, the effect of these preventive measures
on PPE ability to prevent viral spread are not well characterized, and caution is
warranted [43,45]. 

Hand hygiene-related dermatitis — Hand hygiene is considered a key tool


against COVID-19. Hand eczema was already an issue among health care
workers and is likely to be an even greater problem with higher rates of hand
washing and glove use during the pandemic [48].

The frequency of irritant contact dermatitis of the hands may be reduced by


frequent usage of emollients, washing with lukewarm water instead of hot water,
and usage of alcohol-based cleansers when hands are not visibly dirty
[42,46,49,50]. Overzealous hand hygiene may cause hand eczema in the
general population as well [51].
The American Academy of Dermatology has released recommendations on
preventing and treating occupationally induced dermatologic conditions during
the COVID-19 pandemic. (See "Irritant contact dermatitis in
adults" and "Chronic hand eczema".)

THERAPEUTIC CONSIDERATIONS DURING THE

PANDEMIC The COVID-19 pandemic has led to necessary

adjustments to the therapeutic approach for some dermatologic diseases.


Considerations for immunosuppressive therapy, phototherapy, and skin cancer
treatment are reviewed here. Various professional organizations have also
released guidelines for clinical care during the pandemic. (See "Society
guideline links: Coronavirus disease 2019 (COVID-19) – Guidelines for
specialty care", section on 'Dermatology'.)

Use of biologic and other immunosuppressive therapies — Biologic and


immunosuppressive therapies play important roles in the management of a wide
variety of dermatologic diseases, such as psoriasis, atopic dermatitis, and other
inflammatory or autoimmune conditions. The risks of these immunomodulatory
therapies in relation to COVID-19 remain unclear. Although it is generally
accepted that most patients without COVID-19 who are already taking
immunosuppressive drugs for dermatologic disease can continue therapy, a
more cautious approach is typically taken for patients who have suspected or
confirmed COVID-19 and patients who are considering starting a new
immunosuppressive therapy. (See 'Patients without COVID-19' below
and 'Patients with presumed or confirmed COVID-19' below.)

Assessment of risk — The uncertainty regarding the impact of biologic and


other immunosuppressive therapies on severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) infection risk and COVID-19 severity makes risk
assessment challenging [52-54]. Specific challenges for risk assessment
include the paucity of data, the various mechanisms of action of
immunosuppressive drugs, and the need to consider patient-specific and
disease-specific morbidity and comorbidities. Some authors have proposed that
the broad immunosuppression induced by small molecule immunosuppressants
(eg, cyclosporine, mycophenolate, azathioprine) may be of greater concern than
the targeted immunosuppression induced by biologic drugs; however, the
relative safety of individual immunosuppressants remains unclear [55].

Consideration of the potential risks of immunosuppressive therapy must also be


balanced with consideration of the detrimental effects on skin disease and
associated conditions that may result from cessation of effective therapies [56].
Cutaneous disease may flare, and occasional patients may not achieve the
same level of response upon the reintroduction of a previously effective biologic
therapy [53,54]. Of note, the long half-lives of some biologic agents mean that
immunosuppressive effects of concern may still persist for some time following
the decision to stop therapy.

Studies evaluating use of immunomodulatory therapies in relation to COVID-19


in patients with dermatologic disease are limited and insufficient for drawing
conclusions on risk in this population [57-59]. It is unclear whether data from
clinical trials that have assessed risk for upper respiratory infections during
biologic therapy for dermatologic disease are applicable to SARS-CoV-2
infection [54,60-62].

In support of the theory that risks of continuing biologic therapy for skin disease
may be low, one retrospective study of 5206 patients in northern Italy treated
with biologic agents for plaque psoriasis between February 20 and April 1,
2020, found no COVID-19-related deaths and only four COVID-19-related
hospitalizations [57]. In addition, a case control study performed in the
Lombardy region of Italy that involved assessment of 1193 patients with
psoriasis treated with biologic or small molecule therapy and approximately 10
million controls between February 21 and April 9,  2020, found higher risks for
testing positive for COVID-19, being self-quarantined at home due to COVID-
19, or being hospitalized due to COVID-19 among psoriasis patients receiving
biologic therapy compared with controls but did not find statistically significant
increases in risk for intensive care unit admission or dying in this population
[58].

Although the potential for a beneficial effect of biologic inhibitors tumor necrosis
factor (TNF)-alpha or interleukin (IL) 17 in COVID-19 has been proposed based
upon the theory that some immunosuppressive drugs might have inhibitory
effects on damaging immune response that is thought to contribute to organ
damage in COVID-19, this has not been proven [63-66]. Data on IL-6 pathway
inhibitors is reviewed separately. (See "Coronavirus disease 2019 (COVID-19):
Epidemiology, virology, and prevention" and "Coronavirus disease 2019
(COVID-19): Management in hospitalized adults", section on 'IL-6 pathway
inhibitors'.)

Patients without COVID-19 — Decisions on the use of immunosuppressive


therapies in patients without signs or symptoms of COVID-19 during the global
pandemic should be made on a case-by-case basis and in conjunction with the
patient. This may involve review of the patient's comorbidities, severity of the
disease originally being treated, limited available data, expert opinion, local
recommendations, and patient preference.

Continuation of immunosuppressive therapies — Based upon an absence


of evidence that suggests benefit of discontinuing immunosuppressive therapies
in patients without COVID-19 and the potential detrimental effects of
discontinuing effective therapies, the continuation of biologic and small
molecule immunosuppressants for dermatologic disease is generally
considered a safe and appropriate option for patients who do not have
suspected or documented COVID-19. Examples of societies that support this
approach include the American Academy of Dermatology [67], National
Psoriasis Foundation [68], International Psoriasis Council [69], British Academy
of Dermatology [70], and International League of Dermatological Societies [71].
Initiation of immunosuppressive therapies — Routine avoidance of initiating
a new immunosuppressive therapy for dermatologic disease in patients without
COVID-19 is not considered necessary. However, given that some uncertainty
remains regarding the effects of immunosuppressive therapies on COVID-19,
the decision to start a new immunosuppressive drug for dermatologic disease
should be taken carefully, involving a case-specific review of the potential risks
and benefits of therapy. In particular, for patients perceived to be at increased
risk for severe COVID-19, it may be prudent to consider deferring
immunosuppressive treatments in favor of other therapies [67].
(See "Coronavirus disease 2019 (COVID-19): Epidemiology, virology, and
prevention".)

Some authors have proposed testing for SARS-CoV-2 infection or immunity


prior to initiation of immunosuppressive therapies [72]. However, the value of
this approach is unclear.

Patients with presumed or confirmed COVID-19 — Active infection is an


accepted indication for discontinuation and avoidance of initiation of
immunosuppressive therapies. Some professional societies, including the
American Academy of Dermatology, have issued statements that recommend
discontinuation of immunosuppressive drugs in patients who develop COVID-
19, although this remains an area of debate [73]. This approach may be the
appropriate default for most patients with confirmed COVID-19.
Immunosuppressive therapy may be resumed, if needed, following complete
recovery from COVID-19.

However, given the uncertainty about the effects of various


immunosuppressants on the course of COVID-19, the decision to discontinue
treatment in a patient with COVID-19 should be made on a case-by-case basis.
Other factors that may influence the decision to cease treatment may include
the severity of COVID-19, the potential that biologic treatment may reduce risk
of cytokine storm, and the potential negative ramifications of treatment
cessation on flaring immunologic activity, including both dermatologic disease
and comorbidities.

Phototherapy — In-office phototherapy typically involves frequent clinic visits,


potentially increasing exposure of patients and clinical staff to SARS-CoV-2.
Thus, the risks and benefits of office-based phototherapy should be weighed
carefully for individual patients. 

Home phototherapy is an alternative that may be the preferred method of


phototherapy during the pandemic but may not be feasible for all patients. If in-
office phototherapy is necessary, careful precautions, including screening for
symptoms, limiting visitors, personal protective equipment (PPE) use, and
equipment disinfection, should be taken to reduce the risk of transmission of
infection [74,75]. Alternatives to phototherapy should also be considered.
(See "Coronavirus disease 2019 (COVID-19): Infection control in health care
and home settings", section on 'Infection control in the health care setting'.)

Skin cancer — Many full body skin examinations, biopsies, and skin cancer
excisions are being postponed due to the COVID-19 pandemic, which may lead
to delays in diagnosis and treatment. Triage and management strategies during
the COVID-19 pandemic for melanoma, advanced squamous cell carcinoma,
and advanced basal cell carcinoma have been developed by several groups,
including the National Comprehensive Cancer Network, the European Society
for Medical Oncology, and the American College of Mohs Surgery, with
deferment of surgery or prompt surgery dependent upon the type of lesion and
reason for the visit [76-78]. The United States Cutaneous Lymphoma
Consortium has published recommendations for the treatment of cutaneous
lymphomas during the COVID-19 pandemic [79].

For patients with advanced melanoma and nonmelanoma skin cancers who are
under treatment, there are no recommendations to cease skin cancer-related
systemic therapies [80,81]. However, the decision regarding the continuation or
initiation of systemic targeted therapies or immunotherapies must be made on a
case-by-case basis, after careful evaluation of benefits versus risks.

General and specific issues related to the care of cancer patients during the
pandemic are discussed elsewhere. (See "Coronavirus disease 2019 (COVID-
19): Cancer care during the pandemic".)

DELIVERY OF CARE DURING THE PANDEMIC Local

guidelines on the performance of routine, nonurgent medical care during the


pandemic differ and continue to evolve. In many settings, the pandemic has led
to increased use of telemedicine for dermatologic care (ie, teledermatology). In
scenarios in which in-person care remains necessary or appropriate,
precautions to limit risk for transmission of infection are indicated.
(See 'Telemedicine'below and 'In-person care' below and "Society guideline
links: Coronavirus disease 2019 (COVID-19) – Guidelines for specialty care",
section on 'Dermatology'.)

Telemedicine — Telemedicine provides an opportunity to provide care while


reducing risk for exposure of clinicians, staff, and patients to individuals with
COVID-19 [82,83]. Both synchronous (eg, simultaneous, two-way
communication between the patient and clinician via telephone or
videoconferencing) and asynchronous (eg, store-and-forward transmission of
images for later assessment by the clinician) modalities have been utilized for
teledermatology care [84]. A structured triage process may be helpful for
identifying patients who require in-person, rather than a telemedicine, visit
[85,86]. 

Telemedicine may also be an appropriate option for inpatient dermatologic care


in some scenarios. The Society of Dermatology Hospitalists has produced an
algorithm to guide triaging of consultations and the performance of safe
inpatient dermatologic care [87]. 

Concerns have been raised over privacy and security of telemedicine [88,89].
The platform selected should be compliant with local privacy regulations. Due to
the COVID-19 pandemic, some regulatory bodies have relaxed or waived rules
to allow more flexibility in telemedicine [90].

In-person care — In-person visits should be performed with appropriate


infection control precautions. This typically includes at least patient screening
and use of appropriate personal protective equipment (PPE) [91-93]. Best
practices for infection control in the clinical setting are reviewed separately.
(See "Coronavirus disease 2019 (COVID-19): Infection control in health care
and home settings", section on 'Infection control in the health care setting'.)

Although the risk of transmission of severe acute respiratory syndrome


coronavirus 2 (SARS-CoV-2) through procedures such as dermoscopy remains
unclear, clinicians should be cognizant about the potential for transmission
through equipment that may come into contact with multiple patients. In regards
to dermoscopy, noncontact dermoscopy is the preferred form of dermoscopy
during the pandemic. Examples of additional suggestions for reducing risk for
disease transmission through dermoscopy have included disinfection of the
dermatoscope with alcohol for at least one minute prior to and following
examination, use of polyvinyl chloride food wrap or glass slide between the lens
and lesion, use of alcohol gel as an interface medium, and use of disposable
dermoscopic lens covers [94-96].

REGISTRIES Multiple registries have been developed, with the goal of

increasing knowledge of the dermatologic manifestations and impact of COVID-


19 in patients with dermatologic disease. Examples include:
●General dermatologic manifestations of COVID-19 or patients with any
pre-existing dermatologic condition:
•American Academy of Dermatology/International League of
Dermatological Societies COVID-19 Registry
●Psoriasis:
•Psoriasis Registry for Outcomes, Therapy, and Epidemiology of
COVID-19 Infection (PsoPROTECT)
•Surveillance Epidemiology of Coronavirus (COVID-19) Under
Research Exclusion Registry (SECURE-Psoriasis Registry)
●Atopic dermatitis:
•Surveillance Epidemiology of Coronavirus (COVID-19) Under
Research Exclusion Registry (SECURE-AD Registry)
●Alopecia:
•Surveillance Epidemiology of Coronavirus (COVID-19) Under
Research Exclusion Registry (SECURE-Alopecia Registry)
●Hidradenitis suppurativa:
•Global Hidradenitis Suppurativa COIVD-19 Registry
●Acral changes in the pediatric population:
•COVID Acral Ischemia/Perniosis in Children Registry
Disease registries for rheumatologic diseases are reviewed separately.
(See "Coronavirus disease 2019 (COVID-19): Care of patients with systemic
rheumatic disease during the pandemic", section on 'Disease registries'.)
SUMMARY AND RECOMMENDATIONS

●Multiple skin manifestations have been described in patients with


confirmed or suspected severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2) infection. These include a morbilliform rash; urticaria;
pernio-like, acral lesions; livedo-like, vascular lesions; and vesicular,
varicella-like eruptions. A severe multisystem inflammatory syndrome with
mucocutaneous, systemic, laboratory, and imaging findings of atypical,
severe Kawasaki disease has also been reported in children and
adolescents with coronavirus disease 2019 (COVID-19). (See 'Cutaneous
manifestations of COVID-19' above and "Coronavirus disease 2019
(COVID-19): Multisystem inflammatory syndrome in children".)
●Skin injury, mechanical/friction dermatitis, and hand irritant contact
dermatitis due to personal protective equipment (PPE) and hand hygiene
measures have been reported in the majority of health care workers
involved in the care of patients with COVID-19. Use of barrier films or
dressings at pressure points of PPE and frequent use of emollients after
hand washing may help reduce skin damage and irritation.
(See 'Dermatologic conditions related to COVID-19 pandemic'above.)
●The COVID-19 pandemic has contributed to the need to adjust aspects of
dermatologic care. Examples include adjustments in the approach to
immunosuppressive treatment, phototherapy, skin cancer treatment, and
routine clinical care. (See 'Therapeutic considerations during the
pandemic' above and 'Delivery of care during the pandemic' above.)
●The impact of immunosuppressive therapies for dermatologic disease on
risk for SARS-CoV-2 infection and risk for complications of COVID-19 is
unclear. The decision to continue or start immunosuppressive therapy for
dermatologic disease during the pandemic should be made on a case-by-
case basis. Examples of important factors to consider include the patient's
infection status, the immunosuppressant under consideration, and the
impact of treatment cessation on the dermatologic disease and
comorbidities. (See 'Therapeutic considerations during the
pandemic' above.)
●Given the absence of evidence indicating benefit of discontinuing
immunosuppressive therapies in patients without COVID-19, continuation
of immunosuppressive therapy for dermatologic disease is considered a
safe and appropriate option for this population. The decision to start a new
immunosuppressive drug should include careful consideration of potential
risks and benefits of therapy. For patients with risk for severe COVID-19, it
may be appropriate to defer immunosuppressive treatments in favor of
other therapies. (See 'Patients without COVID-19'above.)
●Active infection is an accepted indication for discontinuation and
avoidance of initiation of immunosuppressive therapies, and some
professional organizations, including the American Academy of
Dermatology, have issued statements recommending discontinuation of
immunosuppressive drugs for cutaneous disease in patients who develop
COVID-19. Given the paucity of evidence on risks and benefits of
discontinuation, the decision to continue or discontinue immunosuppressive
treatment in patients with presumed or confirmed COVID-19 may be made
on a case-by-case basis. If discontinued, immunosuppressive therapies
may be resumed upon complete recovery form COVID-19. (See 'Patients
with presumed or confirmed COVID-19' above.)
●The COVID-19 pandemic has contributed to increased use of telemedicine
for routine clinical care. When in-person visits are performed, appropriate
infection control precautions should be implemented. (See 'Delivery of care
during the pandemic' above.)

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