| Literature DB >> 34235511 |
L N Schwartzberg1, S Advani2, D C Clancy1, A Lin3, J L Jorizzo4,5.
Abstract
BACKGROUND: Infection with COVID-19 is characterized by respiratory, gastrointestinal and neurologic symptoms. However, limited evidence exists of the involvement of the integumentary system among COVID-19 patients and evidence suggests that these symptoms may even be the first presenting sign.Entities:
Keywords: evidence‐based dermatology; infection; virology
Year: 2021 PMID: 34235511 PMCID: PMC8250095 DOI: 10.1002/ski2.20
Source DB: PubMed Journal: Skin Health Dis ISSN: 2690-442X
FIGURE 1PRISMA Flow Diagram
Study information and patient population
| First author | Country | Type of article | Number of patients | How patients tested positive | Age | Gender |
|---|---|---|---|---|---|---|
| Hassan, K | Scotland | Case Report | 1 | RT‐PCR | 46 | F |
| Suter, P | Switzerland | Case Report | 1 | RT‐PCR | 42 | M |
| Shanshal, M | Iraq | Case Report | 1 | RT‐PCR | 35 | F |
| Lorenzo‐Villalba, N | France | Case Series | 2 | RT‐PCR | 57 | F |
| Freeman, E | International Registry | Case Series | 23 | (14) PCR, (5) antibody testing, and (4) unknown assay | 41 median | 11 F12 M |
| Lagziel, T | USA | Case Report | 1 | RT‐PCR | 58 | F |
| Eka Putraa, B | Indonesia | Case Report | 1 | RT‐PCR | 29 | M |
| Sakaida, T | Japan | Case Report | 1 | RT‐PCR | 52 | F |
| de‐Medeiros, V | Brazil | Case Report | 1 | RT‐PCR | 55 | F |
| Rivera‐Oyola, R | USA | Case Series | 2 | SARS‐CoV‐2 rapid respiratory panel | 6060 | MF |
| Gianotti R | Italy | Case Series | 3 | RT‐PCR | 598989 | FFM |
| Magro C | USA | Case Series | 3 | RT‐PCR | 326640 | M |
| Sachdeva M | Italy | Case Series | 3 | RT‐PCR | 717772 |
|
| Freeman, E | International Registry | Case Series | 171 | RT‐PCR | 44 median | 93 F78 M |
| Dalal, A | India | Observational Study | 13 | RT‐PCR | 39.3 mean | Unspecified |
| Elsaie, ML | Saudi Arabia | Case Report | 1 | RT‐PCR | 57 | M |
| Ho, B | United Kingdom | Case Report | 1 | RT‐PCR | 79 | F |
| Papamichalis, P | Greece | Case Report | 1 | RT‐PCR | 68 | M |
| Fernandez‐Nieto, L | Spain | Prospective Study | 24 | RT‐PCR | 49.5 median | 18 F6 M |
| Diaz‐Guimaraens, B | Spain | Case Report | 1 | RT‐PCR | 48 | M |
Only includes patients reported in the study who were confirmed COVID‐19 positive and had dermatologic signs.
Number of patients with each cutaneous sign
| Dermatologic diagnosis | Number of patients with skin sign | Percentage of patients with skin sign |
|---|---|---|
| Pernios | 54 | 16.56% |
| Morbilliform exanthem | 44 | 13.50% |
| Vesicular eruption | 43 | 13.19% |
| Urticaria | 32 | 9.82% |
| Erythematous exanthem | 26 | 7.98% |
| Papulosquamous eruption | 18 | 5.52% |
| Retiform purpura | 12 | 3.68% |
| Livedo reticularis‐like lesions | 9 | 2.76% |
| Grover's‐like eruption | 9 | 2.76% |
| Symptom of pruritis without physical sign | 8 | 2.45% |
| Acrocyanosis | 8 | 2.45% |
| Purpura | 8 | 2.45% |
| Acral desquamation | 8 | 2.45% |
| Petechiae | 8 | 2.45% |
| Dengue‐like eruption | 8 | 2.45% |
| Pressure ulcers | 6 | 1.84% |
| Livedo racemosa | 5 | 1.53% |
| Bullous dermatitis | 4 | 1.23% |
| Erythroderma | 4 | 1.23% |
| Erythema nodosum | 3 | 0.92% |
| Aphthous stomatitis | 2 | 0.61% |
| Milaria rubra | 2 | 0.61% |
| Telogen effluvium | 1 | 0.31% |
| Transient acantholytic dermatosis | 1 | 0.31% |
| Herpes zoster | 1 | 0.31% |
| Multisystem inflammatory syndrome | 1 | 0.31% |
| Acneiform eruption | 1 | 0.31% |
FIGURE 2Frequency of Cutaneous Findings Illustrated in Their Common Anatomic Locations
FIGURE 3Percent of Skin Findings per Anatomic Location
Biopsy specimen and dermatopathology
| First author | Cutaneous diagnosis | Skin biopsy |
|---|---|---|
| Freeman, E | Pernios (1) | Mild vacuolar interface dermatitis with dense superficial and deep lymphocytic inflammation, consistent with pernio versus connective tissue disease. No thrombi were noted. |
| Lagziel, T | Bullous interface dermatitis (1) | Detached epidermis with a ‘basket‐weave’ stratum corneum, separated at the dermal‐epidermal junction. Spongiosis and basilar vacuolar changes with rare dyskeratotic cells were present. Superficial dermal edema was also present |
| Sakaida, T | Erythematous cutaneous eruption (1) | slight liquefaction with perivascular and periadnexal mixed cell infiltrations from the papillary dermis to the deep subcutaneous tissue |
| Petechiae (1) | Liquefaction and perivascular mixed cell infiltrations, including histiocytes and neutrophils | |
| Rivera‐Oyola, R | Viral exanthem (1) | Mild perivascular infiltrate of mononuclear cells surrounding vessels in the superficial dermis. The epidermis showed scattered foci of hydropic changes, along with minimal acanthosis, slight spongiosis, and foci of parakeratosi |
| Gianotti R | Viral exanthem (2) | Superficial perivascular dermatitis with slight lymphocytic exocytosis. Swollen thrombosed blood vessels with neutrophils, eosinophils and nuclear debris were found within the dermis |
| Transient Acantholytic Dermatosis (1) | Superficial perivasascular vesicular dermatitis with nests of Langerhans cells within the epidermis. Focal acantholytic suprabasal clefts, dyskeratotic and ballooning keratinocytes and a patchy band‐like infiltration with occasional necrotic keratinocytes | |
| Magro C | Retiform purpura (1) | Thrombogenic vasculopathy with extensive necrosis of the epidermis and adnexal structures, including the eccrine coil. Interstitial and perivascular neutrophilia with leukocytoclasia. Considerable depositions of C5b‐9 within microvasculature |
| Purpura (1) | Superficial vascular ectasia and an occlusive arterial thrombus within the reticular dermis. No surrounding inflammation. Extensive vascular deposits of C5b‐9, C3d and C4d (Figure 6D) within the dermis, with marked deposition in an occluded artery | |
| Livedo racemosa (1) | Perivascular lymphocytic infiltrate in the superficial dermis with deeper seated small thrombi within rare venules of the deep dermi. No clear vasculitis. Significant vascular deposits of C5b‐9 and C4d | |
| Freeman, E | Retiform purpura (3); livedo racemosa (2), livedo Reticularis (1) | Thrombotic vasculopathy |
| Pressure injury (1) | Thrombotic vasculopathy | |
| Grover's‐like eruption (1) | Granulomatous dermatitis with increased central mucin deposition | |
| Papulosquamous eruption (2) | Spongiosis and dermal inflammation | |
| Palpable purpura (1) | Leukocytoclastic vasculitis | |
| Pernio‐like lesions (1); morbilliform exanthem (2) | Vacuolar interface dermatitis, subepidermal edema, and superficial and deep lymphocytic inflammation | |
| Fernandez‐Nieto, D | Vesicular cutaneous eruption (2) | Intraepidermal vesicles with mild acantholysis and ballooned keratinocytes; epidermal detachment and confluent keratinocytic necrosis, fibrinoid material with acute inflammation |
| Diaz‐Guimaraens, B | Petechiae (1) | a superficial perivascular lymphocytic infiltrate with abundant erythrocyte extravasation and focal papillary edema, along with focal parakeratosis and isolated dyskeratotic cells. No features of thrombotic vasculopathy were present |
Quality assessment using the NIH case series assessment tool
| First author | Was the study question or objective clearly stated? | Study population clearly and fully described including a case definition | Cases consecutive | Subjects comparable | Intervention clearly described | Outcome measured clearly defined, valid, reliable and implemented consistently | Was length of follow‐up adequate? | Statistical methods well describe? | Were results well described? | Overall rating | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Dalal | Yes | Yes | Yes | Yes | Yes | Yes | Yes | NA | Yes | Good | |
| de‐Mederios | Yes | NA | NA | NA | Yes | Yes | Yes | NA | Yes | Good | |
| Elsaie | Yes | Yes | CD | CD | Yes | Yes | Yes | NA | Yes | Fair | |
| Freeman | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Good | |
| Freeman | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Good | |
| Gianotti | Yes | No | CD | CD | Yes | Yes | Yes | NA | Yes | Good | |
| Hassan | Yes | Yes | NA | NA | Yes | Yes | CD | NA | Yes | Fair | |
| Ho | Yes | No | CD | CD | Yes | No | CD | NA | Yes | Fair | |
| Khurana | Yes | No | NA | NA | CD | Yes | CD | NA | Yes | Fair | |
| Lagziel | Yes | Yes | NA | NA | Yes | Yes | Yes | NA | Yes | Good | |
| Lorenzo‐Villaba | Yes | Yes | CD | CD | Yes | Yes | CD | NA | Yes | Fair | |
| Magro | Yes | Yes | CD | CD | Yes | Yes | Yes | NA | Yes | Good | |
| Papamichalis | Yes | Yes | NA | NA | Yes | Yes | Yes | NA | Yes | Good | |
| Putra | Yes | Yes | NA | NA | Yes | Yes | CD | NA | Yes | Fair | |
| Rivera‐Oyola | Yes | No | NA | NA | CD | Yes | CD | NA | Yes | Fair | |
| Sachdeva | Yes | No | CD | CD | Yes | No | CD | NA | Yes | Fair | |
| Sakaida | Yes | No | NA | NA | CD | Yes | CD | NA | Yes | Fair | |
| Sanchez | Yes | No | NA | NA | Yes | Yes | CD | NA | Yes | Good | |
| Shanshal | No | Yes | NA | NA | Yes | No | CD | NA | Yes | Fair | |
| Suter | Yes | Yes | NA | NA | Yes | Yes | Yes | NA | Yes | Good | |
Recent reports excluded in the review
| First author | Patient age and gender | Cutaneous manifestation and location | Notes |
|---|---|---|---|
| Goon | 82 years old (yo) F | Morbilliform exanthem; vesicles on acral surfaces; tense bullae on the trunk and limbs | Patient started out with the morbilliform exanthem and vesicular dermatitis on the acral surfaces, but weeks later developed tense bullae consistent with classic bullous pemphigoid. Patient also had cardiac comorbidities. |
| Patel | 78 yo F | Morbilliform exanthem; vesicles and urticaria on trunk and malar cheeks | Patient had mild symptoms typical of COVID‐19. One week prior to symptoms, patient developed the cutaneous signs. One week after symptom onset, patient's exanthem began to desquamate. |
| Cepeda‐Valdes | 50yo F and 20yo M | Urticarial vasculitis on lower extremities | Patients were otherwise asymptomatic. |
| Danarti | 50 yo M | Follicular eruption on upper extremities, neck, and trunk | Patient was otherwise asymptomatic. |
| Bosch‐Amate | 71 yo F | Cutaneous small vessel vasculitis on lower extremities | Cutaneous signs started 1 week after COVID‐19 symptoms. Patient was hospitalized for COVID‐19 pneumonia. |
| Tamai | 54 yo M, 24 yo M, 81 yo F | Erythematous papules on trunk and extremities | Patients were otherwise asymptomatic. |
| Adekiigbe | 47yo M | Gangrene of the toes | Notably, the patient also had diabetes and developed the purpuric toes 11 days after symptom onset. The gangrene required management with amputation. |
| Abasaeed | 40yo M | Angioedema of the lips and periorbital area; truncal urticaria | The patient also experienced shortness of breath and fever. |
| Rubin | 27 yo F | Chilblain‐like lesions with hemorrhagic bullae on the bilateral toes | The patient also experienced anosmia and ageusia. |
| Vanaparthy | 63 yo F | Raynaud's phenomenon | The patient also had mild COVID‐19 symptoms. |
| Iancu | 41 yo F | Morbilliform exanthem | Disseminated exanthem erupted 15 days after treatment of COVID‐19. Medications used included hydroxychloroquine, azithromycin, and lopinavir/ritonavir. |
| Rotman | 62 yo F | Calciphylaxis and thrombotic retiform purpura of the lower extremities | Notably, the patient also had end‐stage renal disease. The patient passed away weeks after onset. |