MIS-C, inherited metabolic diseases and methylmalonic acidemia: a case report and review of the literature (preprint)

Bacground Methylmalonic acidemia (MMA) secondary to mutase deficiency, mut0, is an inborn error of metabolism causing complete enzyme deficiency. Multisystem Inflammatory Syndrome in Children (MIS-C) is a hyperinflammatory syndrome characterized by fever, inflammation, multiorgan impairment that manifests 14–60 days after the SARS-CoV-2 infection in patients aged < 21 years. Case presentation We describe the clinical case of a 2-year-old child with MMA secondary to mutase deficiency, with the documented homozygous mutation c.2179 C > T of MMUT gene, associated to mut0 phenotype. One month after SARS-CoV-2 infection, he presented fever, rash, significant increase of C-reactive protein (CRP), ferritin, triglycerides, (interleukin) IL-6, PRO-BNP, compatible with the diagnosis of MIS-C. He was treated with intravenous immunoglobulins (2gr/Kg), methylprednisolone (2 mg/Kg/day), with rapid clinical improvement. Ten days later, he showed the worsening of clinical conditions, with the recurrence of fever, vasculitic rash with palmoplantar extension, further increase of ferritin (1033 ug/l), IL-6 (146 pg/ml), PRO-BNP (5117 pg/ml), triglycerides, anemia, thrombocytopenia, metabolic acidosis with hyperlactatemia (180 mg/dl), increased urinary methylmalonic acid (200 mmol/mCreat), multiorgan failure. He was treated with sodium bicarbonate, thiamine, coenzyme Q, vitamin C, methylprednisolone and anakinra (2 mg/Kg/day). Three days after the start of anakinra, he showed a significant improvement of clinical and biochemical parameters and defervescence. 20 days later, a sepsis from Staphylococcus Aureus and Candida Albicans required the interruption of anakinra, with the worsening of the clinical and haematological parameters and the exitus. Conclusions Only a few cases of patients with inherited metabolic diseases (IMD) and MIS-C are described. However, to our knowledge, this is the first case of MIS-C in MMA described. The description of these clinical cases is a precious lesson for pediatricians to manage IMD therapeutic emergencies. Anakinra must be considered as a safe treatment of choice in IMD patients with MIS-C. The use of anakinra in patients with a severe form of MMA is safe and can be employed to treat MIS-C, gaining a substantial clinical and biochemical improvement.

Pityriasis rosea as a cutaneous manifestation associated with SARS-CoV-2 infection: case report / Pitiriasis rosada como manifestación dermatológica de infección por SARS-CoV-2: a propósito de un caso

Las manifestaciones cutáneas relacionadas a la infección por el coronavirus SARS-CoV-2, causante de COVID-19, se han descrito entre el 0,2% y 20,4% de las personas que cursan con esta enfermedad. Las más frecuentemente descritas son: lesiones maculopapulares (47%), lesiones acrales eritematosas con vesículas o pústulas (pseudoperniosis) (19%), urticariales (19%), lesiones vesiculosas (9%) y livedo/necrosis (6%). En particular, la pitiriasis rosada es una dermatosis autolimitada de etiología desconocida, sin embargo, se ha visto asociada a la infección por SARS-CoV-2, con algunos reportes de casos en la literatura. El mecanismo fisiopatológico de las lesiones cutáneas en COVID-19 no es claro, y se han planteado algunas teorías, entre las cuales está el papel que juega la enzima convertidora de angiotensina 2 (ACE2) utilizada por el virus para infectar las células, los infiltrados linfocíticos, los depósitos de factores del complemento en la piel, y la reactivación de virus latentes como los herpes virus humanos. Se presenta el caso de una paciente con pitiriasis rosada asociada a COVID-19 y se describen los casos reportados hasta la fecha

Recurrent reactive infectious mucocutaneous eruption in a male adult patient associated with Mycoplasma pneumoniae, SARS-CoV-2 and rhinovirus.

We present a case of a man in his early 30s who developed four episodes of reactive infectious mucocutaneous eruption (RIME), in association with different infectious pathogens.RIME is a recently implemented term to describe mucocutaneous eruptions associated with respiratory pathogens. These eruptions are characterised by predominant mucosal involvement of two or more mucous membranes and limited cutaneous involvement. The disease course and prognosis are mostly favourable, especially in recurrent episodes of RIME in the same patient. In recurrent episodes of RIME, Mycoplasma pneumoniae is often identified as the infectious trigger in the first episode.

Severe rash after COVID-19 vaccination.

The patient's recent vaccine was the most remarkable thing about his medical history.

Fever, Rash, and Cough in a 7-Year-Old Boy.

A 7-year-old boy presented to the emergency department with fever, cough, congestion, abdominal pain, myalgias, and morbilliform rash. Several aspects of the patient's history, including recent travel, living on a farm, exposure to sick contacts, and new medications, resulted in a wide differential diagnosis. Initial laboratory testing revealed leukocytosis with neutrophilia and elevated atypical lymphocytes, but did not reveal any infectious causes of illness. He was discharged from the hospital, but then represented to the emergency department a day later with worsening rash, continued fever, abdominal pain, and poor intake. He was then admitted. A more comprehensive laboratory evaluation was initiated. During this hospital course, the patient's physical examination changed when he developed head and neck edema, and certain laboratory trends became clearer. With the assistance of several specialists, the team was able to reach a more definitive diagnosis and initiate treatment to appropriately manage his condition.

COVID 19-associated chilblain-like acral lesions among children and adolescents: an Italian retrospective, multicenter study.

BACKGROUND: Since the COVID-19 pandemic started, great interest has been given to this disease, especially to its possible clinical presentations. Besides classical respiratory symptoms, dermatological manifestations occur quite often among infected and non-infected patients, particularly in children. A prominent IFN-I response, that is generally higher in children compared to adults, may not only cause chilblain lesions, but it could also prevent infection and viral replication, thus justifying the negative swab results, as well as the absence of relevant systemic symptoms in positive cases. Indeed, reports have emerged describing chilblain-like acral lesions in children and adolescents with either proven or suspected infection. METHODS: Patients aged from 1 to 18 years old were enrolled in this study from 23 Italian dermatological units and were observed for an overall period of 6 months. Clinical pictures were collected along with data on the location and duration of skin lesions, their association with concomitant local and systemic symptoms, presence of nail and/or mucosal involvement, as well as histological, laboratory and imaging findings. RESULTS: One hundred thirty-seven patients were included, of whom 56.9% were females. Mean age was 11.97±3.66 years. The most commonly affected sites were the feet (77 patients, 56.2%). Lesions (48.5%) featured cyanosis, chilblains, blisters, ecchymosis, bullae, erythema, edema, and papules. Concomitant skin manifestations included maculo-papular rashes (30%), unspecified rashes (25%), vesicular rashes (20%), erythema multiforme (10%), urticaria (10%) and erythema with desquamation (5%). Forty-one patients (29.9%) reported pruritus as the main symptom associated with chilblains, and 56 out of 137 patients also reported systemic symptoms such as respiratory symptoms (33.9%), fever (28%), intestinal (27%), headache (5.5%), asthenia (3.5%), and joint pain (2%). Associated comorbid conditions were observed in 9 patients presenting with skin lesions. Nasopharyngeal swabs turned out positive in 11 patients (8%), whereas the remainder were either negative (101, 73%) or unspecified (25, 18%). CONCLUSIONS: COVID-19 has been credited as the etiology of the recent increase in acro-ischemic lesions. The present study provides a description of pediatric cutaneous manifestations deemed to be potentially associated with COVID-19, revealing a possible association between acral cyanosis and nasopharyngeal swab positivity in children and teenagers. The identification and characterization of newly recognized patterns of skin involvement may aid physicians in diagnosing cases of asymptomatic or pauci-symptomatic COVID patients.

Ponatinib-Associated Cutaneous Eruptions-A Case Series and Review of Clinicopathologic Findings.

ABSTRACT: Ponatinib is a third-generation tyrosine kinase inhibitor used to treat chronic myeloid leukemia and Philadelphia-positive acute lymphoblastic leukemia. Cutaneous toxicities are a commonly reported side effect of ponatinib treatment with "rash" being one of the most common. Specific subtypes are infrequently reported, but include hyperkeratotic, folliculocentric, ichthyosiform, and pityriasis rubra pilaris-like eruptions. Herein, we highlight the clinicopathologic features of 2 cases of ponatinib-induced pityriasis rubra pilaris-like eruptions. We also classify the clinical and histopathologic features of all previously reported ponatinib-associated eruptions in the literature and discuss treatment and potential diagnostic pitfalls.

A case of aleukemic leukemia cutis after COVID-19 infection presenting as facial rash.

Aleukemic leukemia cutis (ALC) is a rare condition that is characterized by leukemic cells in the skin before presenting in the peripheral blood or bone marrow. We report a case of a 43-year-old woman who underwent assessment for bilateral facial nodules arising 1 month after COVID-19 infection. A punch biopsy specimen showed a malignant neoplasm primarily composed of immature blasts dissecting through the collagen in the dermis, concerning for myeloid sarcoma versus leukemia cutis. Bone marrow and blood specimens were negative for hematologic malignancy. The patient was appropriately treated with chemotherapy and is recovering well. This report highlights an interesting case of ALC following COVID-19 infection presenting as an isolated facial rash. Whether there is a true relationship between the patient's COVID-19 infection and her abrupt presentation of leukemia remains unclear, but we present this case regardless, in an effort to highlight a potentially unique association requiring further study.

Cutaneous manifestations of Coronavirus Disease 2019.

BACKGROUND: COVID-19 has been linked to a variety of dermatological conditions. OBJECTIVE: To determine the presence of various cutaneous manifestations in patients with COVID-19, also to define their features in relation to the systemic symptoms. METHODS: This research enrolled a total of 1206 lab-confirmed COVID-19 individuals at a tertiary-care hospital in Karachi, Pakistan. Expert dermatologists assessed patients for COVID-related skin conditions. COVID-19 severity was categorized as asymptomatic/mild, moderate, or severe. RESULTS: Of the 102 (85.7%) patients with only one cutaneous sign, 26.5% developed maculopapular/morbiliform/erythematous rash; 14.7% urticaria; 9.85% vesicular/pustular exanthem; 14.7% vascular pattern; 12.7% infections, 7.8% miscellaneous and 9.8% late cutaneous findings A longer-lasting vascular pattern was related with an older age and a fatal COVID-19 outcomes (P: 0.000) compared with mild/moderate disease. Most of the retiform purpura presented exclusively with thromboembolic episodes. The moderate severity was correlated with maculopapular/morbiliform/exanthematous phenotype (P: 0.009), whereas urticaria was attributed to asymptomatic/mild disease (0.001) compared with moderate/severe infection. LIMITATIONS: Single-Center and observational study. CONCLUSION: Vascular lesions were correlated with disastrous COVID-19 outcomes, whereas retiform purpura was linked to adverse outcomes. The maculopapular/morbiliform/erythematous rash was associated with moderate severity, while the urticarial rash was linked to milder course compared with moderate/severe severity infection.

Covid-19 skin manifestations: an update.

PURPOSE OF REVIEW: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-19 is a multisystemic disease manifesting mainly with dry cough, fever, and pneumonia and can present with a myriad of cutaneous manifestations. This chapter will review SARS-CoV-2 associated cutaneous findings, including incidence and relevance to the pediatric population. RECENT FINDINGS: The most commonly reported cutaneous findings described for COVID-19 in adults and children were chilblains-like lesions, followed by maculopapular eruption, urticarial lesions, vesicular lesions, and livedoid lesions. Children can also present with erythema multiforme (EM)-like lesions and skin findings associated with multisystem inflammatory syndrome in children (MIS-C). SUMMARY: There are numerous cutaneous manifestations of COVID-19, some of which are unique to children such as EM-like lesions and skin findings for MIS-C. Livedoid lesions do not commonly occur in the pediatric population. In mild cases, supportive care is indicated, whereas severe cases warrant intensive care and hospitalization.

Cutaneous Manifestations in Patients with SARS-CoV-2 Infections.

While SARS-CoV-2 is known to cause pneumonia and acute respiratory distress syndrome (ARDS), many extrapulmonary manifestations of COVID-19 have also been observed. Cutaneous manifestations including erythematous rash, urticaria, and chickenpox-like vesicles have been described in patients with SARS-CoV-2. Six patients, two men and four women, in the age group of 50 to 60 years old, hospitalized with SARS-CoV-2 infection confirmed with real-time polymerase chain reaction (real-time PCR) presented cutaneous manifestations. The rash was confluent, spotty, centrifugal, and non-itchy on the head and torso. It was not hemorrhagic, and no crust or blisters were observed. The results of laboratory tests were normal, and the rash disappeared on its own. Several cases of cutaneous manifestations have been reported in patients with SARS-CoV-2 infection. Further studies are needed in order to assess the skin lesions and determine their association with COVID-19.

Cutaneous manifestations of COVID-19 patients in a Hospital in São Paulo, Brazil, and global literature review.

BACKGROUND: Since the beginning of the COVID-19 pandemic, a myriad of cutaneous manifestations have been described in association with this viral infection. However, in Latin America, this kind of data is still scarce. OBJECTIVE: In this sense, the goal of this study was to describe the dermatological findings observed during SARS-CoV-2 infection, in a Brazilian Hospital. METHODS: This is a cross-sectional, retrospective and descriptive study of 50 cases of new-onset dermatologic symptoms in patients with COVID-19, treated at Hospital Sírio-Libanês, from February to June 2020. RESULTS: The patients (n = 50) were classified into 6 groups, according to the elementary lesions and the statistical analysis was performed. The most common cutaneous lesions were maculopapular eruptions (44%), necrosis, purpura, and livedo (32%), urticarial lesions (12%), pseudochilblains (4%) and papular-vesicular eruption (4%). In 46% of the patients the cutaneous lesions occurred in association with other symptoms, such as pruritus (38%), pain and burning sensation (8%). Lower limbs were affected in 44% of the cases, followed by the trunk (38%), upper limbs (24%) and face (14%). Cutaneous lesions were mostly found after other COVID-19 systemic symptoms, with a mean period between the viral syndrome and cutaneous signs of 5 days (SD = 6.1 days). STUDY LIMITATIONS: It is a small sample, in a single-center study, with patients exclusively from a private Hospital. CONCLUSIONS: Patients in Brazil have the same proportion of lesions as revealed in other studies in Europa. The compiled data is essential for a better understanding of cutaneous manifestations deemed secondary to COVID.

The Role of Malnutrition on Outocomes of Multisystem Inflammatory Syndrome Due to Covid-19 in Children (preprint)

Background Malnutrition increases the complications and mortality in critically-ill children. A retrospective study was performed to define the role malnutrition on outcomes of multisystem inflammatory syndrome (MIS-C) due to COVID-19 in children.Methods Patients with MIS-C due to COVID-19 were evaluated for demographic features, anthropometric parameters, clinical findings and outcomes. Patients with z scores of body mass index (> 5 years-of-age) and weight-for-age (< 5 years-of-age) < -2 were considered as malnourished. Sarcopenia was defined by total psoas muscle area (tPMA), calculated on abdominal computed tomography (CT) at the level of L3 and L4 vertebrae. The z scores <- 2 for tPMA were considered as sarcopenia. The results of patients with (M+) and without (M-) were compared.Results Twenty-seven patients were included. Forty-four percent (n = 12) of patients had malnutrition. Malnutrition was classified as mild to moderate (1/3), severe (1/3) and overweight (1/3). Eighty-two cases had acute malnutrition. Among MIS-C symptom criteria, rash was significantly higher in M + children (p<0.05). Laboratory investigations showed higher ferritin levels in M + patients (p<0.05). The median tPMA and sarcopenia is significantly higher in M + when compared to M- group (42% vs 7%, p<0.05). The oral feeding time, complication rates and length of hospital stay were similar in both groups (p>0.05).Conclusion Children with MIS-C due to COVID-19 already have mild to severe malnutrition at admission. Rash and higher ferritin levels are more common in patients with malnutrition. In addition to anthropometric parameters, sarcopenia calculated using tPMA can be used to predict malnutrition in critically-ill children.