Skin Manifestations as Early Presenting Symptom of COVID-19 in Acute Myeloid Leukemia

INTRODUCTION

The occurrence of the COVID-19 pandemic caused by a coronavirus (SARS-CoV-2) is one of the biggest challenges currently facing the medical community with more than 20 million cases worldwide. Numerous studies have reported clinical presentations and outcomes of COVID-19 in previously healthy persons. Also, there are a few reports regarding outcomes or presentation of COVID-19 in patients with a history of malignancy and immunosuppressive therapy [1-3].

There are different opinions about the impact of immunosuppressing drugs and disease on the incidence, manifestations, severity, and outcome of COVID-19 in people with malignant diseases compared to non-malignant.  In a Chinese study, it is reported that COVID-19 patients with cancer had a higher risk of respiratory failure and ICU admission [4]. 

Another study in immunosuppressed post-transplantation patients did not show a higher risk of severe events of COVID-19 [5]. The respiratory tract is the primary site of infection for COVID-19 with symptoms ranging from a flu-like symptom to fulminant pneumonia and respiratory failure [6].

The diagnostic assay for SARS-CoV-2-infection by RT-PCR is a gold standard test for diagnosis of COVID-19 which has high specificity and low sensitivity (30–50%) [7]. While the chest CT positive rate was more than 90% in highly suspected cases [8]. So it was recommended to do a lung CT scan as the main diagnostic and screening basis for COVID-19.

Different organs could be affected by COVID-19. There are few descriptions of the cutaneous manifestations of COVID-19. Skin lesions as a manifestation of COVID-19 have been reported in some case reports and case series [9-11]. Most of the reported skin lesions in COVID-19 are urticarial and maculopapular rash that may have many differential diagnoses, such as drug reactions and other viral infections. Various theories have been proposed about the mechanisms of cutaneous manifestations in COVID-19 infection. These could be the direct effect of COVID-19 or might be indirect complications leading to vascular occlusion or damage [12, 13]. One hypothesis is that immune complexes against the viral particles that appear in the skin blood vessels could lead to a type of vasculitis. Also, it could be postulated that Langerhans cells activation due to immune response to the virus, without the direct involvement of keratinocytes, can lead to vasodilation and spongiosis [14]. The purpose of this article is to report two cases of AML with fever and various cutaneous manifestations as presenting symptoms of COVID-19 and provide a literature review of various cutaneous manifestations in patients with COVID-19.

MATERIALS AND METHODS

Patients' demographic, clinical, and laboratory data were gathered from their medical records. Two individuals consented in writing to the use of their data. A review of the literature was conducted to know the documented dermatologic symptoms of COVID-19.

RESULTS AND DISCUSSION

Case-1 

A 56-year-old woman was admitted to the hematology department with pancytopenia an initial diagnosis of acute leukemia. No splenomegaly or lymphadenopathy was detected in clinical examination.

Bone marrow samples were analyzed for morphologic, immunophenotypic, and genetic evaluation, and AML M4 (acute myelomonocytic leukemia) was diagnosed. A normal female karyotype (46, XX) was reported in the routine cytogenetic analysis. Molecular assays were performed, NPM1 mutation and concurrent FLT3-ITD mutation with a low allelic ratio (36%) were detected.

Induction chemotherapy for AML with standard (7 + 3) regimen was started (Cytarabine, 100mg/m2/day in D1-D7 + Idarubicin, 12mg/m2/day in D1-D3). 2 weeks after induction chemotherapy the patient developed prolonged cytopenia, fever, maculopapular rash, and urticaria on the abdomen and legs (Figure 1a). Fever workup was done and empirical antibiotic therapy started. At this time, no positive findings were found in favor of infection in cultures, lung CT scans, and other assessments.

In the following days, the skin lesions progressed as diffuse maculopapular exanthema, palpable purpuric lesions, and hemorrhagic macular rash on the legs which were accompanied by generalized edema, itching, arthralgia, and persistence of neutropenic fever.

After four weeks the imaging was repeated and the second chest CT scan showed bilateral ground-glass and patchy opacities highly suggestive of COVID-19 infection (Figure 1b).

The patient remained cytopenic, and the CRP level was high (ranged 70-120 mg/L). Infection with SARS-CoV-2 was confirmed by RT-PCR and she was transferred to isolation wards in the department of infectious disease. After two weeks, cutaneous manifestation and fever were improved and the bone marrow aspiration/biopsy was in remission with incomplete hematologic recovery.

Case-2

A 42-year-old woman with a diagnosis of AML-M1 was admitted to the hematology department for induction therapy. Her initial CBC included a WBC count of 59000/mm3 with more than 50% blasts in peripheral blood, hemoglobin of 7 g/dL, and a platelet count of 30,000/mm3.

The diagnosis was confirmed based on morphology and immune-phenotyping analysis of bone marrow aspiration. Normal female karyotype (46, XX) with mutated NPM1 and FLT3-ITD was reported in the cytogenetic and molecular study.

Ten days after the end of induction chemotherapy with (7 + 3) regimen, she suffered from maculopapular rash, spreading to the legs that further developed to multiple, diffuse, non-blanching purpura scattered on the distal lower and upper extremities and trunk over a few days (Figure 2a).

She also complained of itching and arthralgia but did not have a cough or any respiratory symptoms. She was febrile with a high level of CRP (77 mg/l) and negative blood cultures and a normal lung CT scan (Figure 2). Twenty days after induction chemotherapy, WBC count of 800/mm3, hemoglobin of 7.4 g/dL, and platelet count of 50,000/mm3 were reported. On day 16^th bone marrow evaluation was hypocellular with less than 5 % blast. Within 12 days from first imaging, the lung CT scan was suggestive of COVID-19 infection (Figure 2b), and she was transferred to isolation wards for supportive therapy but RT-PCR was negative at once. Notably, both patients were in the same room for a week at their initial admission.