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Erythema Infectiosum (Clinical)

Erythema infectiosum is an illness commonly identified by a characteristic rash; it is caused by parvovirus B19. Erythema infectiosum is also known as fifth disease, being 5th in the historical list of rash-causing childhood infectious diseases: measles (1st), scarlet fever (2nd), rubella (3rd), Dukes' disease (4th), and roseola (6th). Transmission is thought to be through contact with contaminated respiratory secretions. Diagnosis is generally clinical, suspected in patients presenting with an erythematous malar rash with circumoral pallor (“slapped cheek”). A rash over the trunk and extremities occurs afterward. The illness is self-limited and has no specific therapy. Complications can occur, however, due to the viral tropism for erythrocyte precursors. Patients with hemoglobinopathies can experience aplastic crisis, while the immunocompromised may have chronic infection producing pure red cell aplasia.

Last updated: May 26, 2023

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion infectiosum is an illness caused by parvovirus B19 Parvovirus B19 Primate erythroparvovirus 1 (generally referred to as parvovirus B19, B19 virus, or sometimes erythrovirus B19) ranks among the smallest DNA viruses. Parvovirus B19 is of the family Parvoviridae and genus Erythrovirus. In immunocompetent humans, parvovirus B19 classically results in erythema infectiosum (5th disease) or “slapped cheek syndrome.” Parvovirus B19, which presents with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever and a characteristic rash Rash Rocky Mountain Spotted Fever.

Epidemiology[1–3]

  • Infection affects all ages but is more common in children between 3 and 15 years of age.
  • Outbreaks Outbreaks Sudden increase in the incidence of a disease. The concept includes epidemics and pandemics. Influenza Viruses/Influenza occur commonly in schools and childcare settings.
  • Occurrences of infection are more frequent in late winter Winter Pityriasis Rosea and early summer.
  • Has no particular geographic or demographic predilection
  • Infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease occur both sporadically and in epidemic clusters.
  • Pregnant women:
    • Should be considered a separate category because of high risks for the fetus in cases of infection during pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
    • 30% lack parvovirus B19 Parvovirus B19 Primate erythroparvovirus 1 (generally referred to as parvovirus B19, B19 virus, or sometimes erythrovirus B19) ranks among the smallest DNA viruses. Parvovirus B19 is of the family Parvoviridae and genus Erythrovirus. In immunocompetent humans, parvovirus B19 classically results in erythema infectiosum (5th disease) or “slapped cheek syndrome.” Parvovirus B19 antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions ( IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis), placing them at risk for infection

Pathophysiology

Mode of transmission[3,4,15]

  • Respiratory secretions via:
    • Saliva Saliva The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptyalin. Salivary Glands: Anatomy
    • Mucus
    • Fomites Fomites Inanimate objects that carry pathogenic microorganisms and thus can serve as the source of infection. Microorganisms typically survive on fomites for minutes or hours. Common fomites include clothing, tissue paper, hairbrushes, and cooking and eating utensils. Adenovirus
  • Contact with infected blood or blood products
  • Vertical/ transplacental transmission Transplacental transmission Zika Virus Infection in nonimmune women (can result in congenital Congenital Chorioretinitis infection)

Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus[3,14,15]

The incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period is 4–21 days.

Pathogenesis[3,7]

  • Initial B19 viral infection:
    • Entry into the upper respiratory tract → viremia Viremia The presence of viruses in the blood. Erythema Infectiosum (prodromal symptoms) 5–10 days from exposure
    • Virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology spreads and is cytotoxic Cytotoxic Parvovirus B19 to rapidly dividing erythroid precursor cells in the bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis → transient ↓ reticulocytes and anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types
    • In healthy individuals: Bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis effect is not clinically significant.
    • In individuals with hematologic conditions: severe anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types/aplastic crisis occurs.
    • In immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship, viremic state can be prolonged.
  • Rash Rash Rocky Mountain Spotted Fever:
  • If a person is immunocompetent, immunity is usually conferred following infection.

Clinical Presentation

Initial prodromal symptoms Initial Prodromal Symptoms Erythema Infectiosum ( viremia Viremia The presence of viruses in the blood. Erythema Infectiosum)[3,5,14,15]

  • Low-grade fever Low-Grade Fever Erythema Infectiosum
  • Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics
  • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
  • Cold-like symptoms
  • Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema)

Later symptoms ( viremia Viremia The presence of viruses in the blood. Erythema Infectiosum resolved)[3,5,14,15]

Complications[4–6,8,13,14]

  • Arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis:
    • Acute symmetric joint pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways (hands, knees, ankles)
    • More common in teenagers and adults (women > men)
    • Up to 10% of children may have stiff joints.
    • Can last 3 weeks or longer
    • No degenerative joint changes
  • Transient aplastic crisis Transient aplastic crisis Parvovirus B19
    • Rapid decline in RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology
    • Seen in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with sickle cell disease Sickle cell disease Sickle cell disease (SCD) is a group of genetic disorders in which an abnormal Hb molecule (HbS) transforms RBCs into sickle-shaped cells, resulting in chronic anemia, vasoocclusive episodes, pain, and organ damage. Sickle Cell Disease, spherocytosis, and other hematologic diseases
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with weakness/ lethargy Lethargy A general state of sluggishness, listless, or uninterested, with being tired, and having difficulty concentrating and doing simple tasks. It may be related to depression or drug addiction. Hyponatremia and pallor.
  • Maternal infection and fetal effects:
    • Rare but a serious infection (leading to fetal RBC destruction), especially when onset is in the 1st 20 weeks of pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
    • Hydrops Hydrops Cholecystitis fetalis: accumulation of fluid in fetal soft tissue Soft Tissue Soft Tissue Abscess and serous cavities associated with elevated risk of fetal death 
  • Chronic infection in immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship:
    • These patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship cannot mount an immune response to viremia Viremia The presence of viruses in the blood. Erythema Infectiosum, increasing the risk for chronic infection.
    • Results in pure red cell aplasia Aplasia Cranial Nerve Palsies (giant pronormoblasts in the bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis) and severe anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types (reduced reticulocytes)
Transient aplastic crisis in parvovirus b19 infection

Transient aplastic crisis in parvovirus B19 infection
Image shows bone marrow cytology. Yellow arrow indicates a giant pronormoblast.

Image: “Parvovirus B19 infection presenting with severe erythroid aplastic crisis during pregnancy in a woman with autoimmune hemolytic anemia and alpha-thalassemia trait: a case report” by Chen CC, Chen CS, Wang WY, Ma JS, Shu HF, Fan FS. License: CC BY 4.0

Diagnosis and Management

Diagnostic approach[4,10,13–15]

  • Diagnosis based on clinical features
  • Additional test(s) in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with signs and symptoms of anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types:
    • Complete blood count (hemoglobin drops by 2 g/dL from baseline)
    • Reticulocyte Reticulocyte Immature erythrocytes. In humans, these are erythroid cells that have just undergone extrusion of their cell nucleus. They still contain some organelles that gradually decrease in number as the cells mature. Ribosomes are last to disappear. Certain staining techniques cause components of the ribosomes to precipitate into characteristic ‘reticulum’ (not the same as the endoplasmic reticulum), hence the name reticulocytes. Erythrocytes: Histology count decreased
  • IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis and IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions antibody testing:[14]
    • For pregnant women with potential exposure to parvovirus B19 Parvovirus B19 Primate erythroparvovirus 1 (generally referred to as parvovirus B19, B19 virus, or sometimes erythrovirus B19) ranks among the smallest DNA viruses. Parvovirus B19 is of the family Parvoviridae and genus Erythrovirus. In immunocompetent humans, parvovirus B19 classically results in erythema infectiosum (5th disease) or “slapped cheek syndrome.” Parvovirus B19:
      • IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions: detected 7–10 days after exposure, indicating acute infection
      • IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis: appears by 2nd day of rash Rash Rocky Mountain Spotted Fever, persisting for life
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who present with transitory aplasia Aplasia Cranial Nerve Palsies of the red blood cells Red blood cells Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology, confirming etiology
    • Severe or persistent arthropathy Arthropathy Osteoarthritis
    • Not utilized in immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship, as they cannot produce detectable antibody levels
  • In immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with pure red cell anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types: Polymerase chain reaction Polymerase chain reaction Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) ( PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR)) for parvovirus B19 Parvovirus B19 Primate erythroparvovirus 1 (generally referred to as parvovirus B19, B19 virus, or sometimes erythrovirus B19) ranks among the smallest DNA viruses. Parvovirus B19 is of the family Parvoviridae and genus Erythrovirus. In immunocompetent humans, parvovirus B19 classically results in erythema infectiosum (5th disease) or “slapped cheek syndrome.” Parvovirus B19 detects infection.
  • To diagnose fetal parvovirus infection: amniotic fluid Amniotic fluid A clear, yellowish liquid that envelopes the fetus inside the sac of amnion. In the first trimester, it is likely a transudate of maternal or fetal plasma. In the second trimester, amniotic fluid derives primarily from fetal lung and kidney. Cells or substances in this fluid can be removed for prenatal diagnostic tests (amniocentesis). Placenta, Umbilical Cord, and Amniotic Cavity PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR)[13,14]
  • Ultrasonography:
    • Used exclusively in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care to diagnose hydrops Hydrops Cholecystitis (performed periodically to look for signs of hydrops Hydrops Cholecystitis)
    • Findings include effusions (pericardial, pleural), skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema, or ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites.
    • To determine anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types in the fetus, doppler Doppler Ultrasonography applying the doppler effect, with frequency-shifted ultrasound reflections produced by moving targets (usually red blood cells) in the bloodstream along the ultrasound axis in direct proportion to the velocity of movement of the targets, to determine both direction and velocity of blood flow. Ultrasound (Sonography) measurement of the fetal middle cerebral artery Middle cerebral artery The largest of the cerebral arteries. It trifurcates into temporal, frontal, and parietal branches supplying blood to most of the parenchyma of these lobes in the cerebral cortex. These are the areas involved in motor, sensory, and speech activities. Cerebrovascular System: Anatomy peak systolic velocity and ductus venosus Ductus venosus Development of the Heart velocity are thought to be more accurate, less invasive, and safer than cord blood sampling.

Treatment

Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion infectiosum is generally a self-limited illness, and treatment is thus supportive.

Supportive care:

  • Arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis: palliative treatment with antiinflammatory medications[7]
    • Ibuprofen Ibuprofen A nonsteroidal anti-inflammatory agent with analgesic properties used in the treatment of rheumatism and arthritis. Nonsteroidal Antiinflammatory Drugs (NSAIDs) 10 mg/kg every 4–6 hours as needed for age ≥ 6 months to < 12 years (maximum, ≤ 2400 mg/day)
    • Acetaminophen Acetaminophen Acetaminophen is an over-the-counter nonopioid analgesic and antipyretic medication and the most commonly used analgesic worldwide. Despite the widespread use of acetaminophen, its mechanism of action is not entirely understood. Acetaminophen 15 mg/kg every 46 hours as needed (maximum, ≤ 4000 mg/day)
  • Transient aplastic crisis Transient aplastic crisis Parvovirus B19: transfusion may be required in severe cases.
    • Transfusion threshold Threshold Minimum voltage necessary to generate an action potential (an all-or-none response) Skeletal Muscle Contraction: hemoglobin 6 g/dL in clinically stable patients Stable Patients Blunt Chest Trauma (consider earlier with signs of hypoperfusion)[8]
    • Packed red blood cells Red blood cells Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology are the transfusion product of choice.
    • 10–15 mL/kg will usually result in a rise in hemoglobin of 2–3 g/dL.[9]
    • A transfusion rate of 2.5 mL/kg/hr avoids circulatory overload issues.
    • Droplet precautions are recommended in addition to standard precautions for hospitalized patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.[14]

Immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with chronic infection and anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types:

  • Reduced dose of immunosuppressive agents:[10]
    • Should be done in consultation with the physician team directing care (e.g., oncology if immunosuppression is due to cancer, infectious disease if due to HIV HIV Anti-HIV Drugs, etc ETC The electron transport chain (ETC) sends electrons through a series of proteins, which generate an electrochemical proton gradient that produces energy in the form of adenosine triphosphate (ATP). Electron Transport Chain (ETC).)
  • Intravenous immunoglobulin ( IVIG IVIG Dermatomyositis) treatment:[14]
    • 400 mg/kg/day for 5 consecutive days[10]
    • May need repeat courses if anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types recurs or parvovirus DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure levels trend upward
    • In patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with HIV HIV Anti-HIV Drugs, there is no consensus for treatment doses of IVIG IVIG Dermatomyositis; maintenance dosage Dosage Dosage Calculation is 0.4 g/kg/day every 4 weeks after initial dose if CD4 cell counts are < 100 cells/µL.[11]
    • Cases refractory to IVIG IVIG Dermatomyositis have been successfully treated with foscarnet Foscarnet An antiviral agent used in the treatment of cytomegalovirus retinitis. Foscarnet also shows activity against human herpesviruses and HIV. Antivirals for Herpes Virus 6 g/day for 5–14 days (high nephrotoxicity Nephrotoxicity Glycopeptides makes this less appealing as a 1st-line therapy).[12]
  • In patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with HIV HIV Anti-HIV Drugs, antiretroviral therapy Antiretroviral therapy Antiretroviral therapy (ART) targets the replication cycle of the human immunodeficiency virus (HIV) and is classified based on the viral enzyme or mechanism that is inhibited. The goal of therapy is to suppress viral replication to reach the outcome of undetected viral load. Anti-HIV Drugs should be started or continued.
  • In severe cases, bone marrow transplantation Bone marrow transplantation Transfer of hematopoietic stem cells from bone marrow or blood between individuals within the same species (homologous transplantation) or transfer within the same individual (autologous transplantation). Hematopoietic stem cell transplantation has been used as an alternative to bone marrow transplantation in the treatment of a variety of neoplasms. Organ Transplantation

Hydrops Hydrops Cholecystitis fetalis (seen with severe fetal anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types that may require intrauterine transfusion): 

  • Serial fetal hemoglobin monitoring through percutaneous umbilical vein umbilical vein Venous vessels in the umbilical cord. They carry oxygenated, nutrient-rich blood from the mother to the fetus via the placenta. In humans, there is normally one umbilical vein. Prenatal and Postnatal Physiology of the Neonate blood draws[13]
  • Intrauterine transfusion:[13]
    • Performed only in fetuses 18–35 weeks’ gestational age Gestational age The age of the conceptus, beginning from the time of fertilization. In clinical obstetrics, the gestational age is often estimated as the time from the last day of the last menstruation which is about 2 weeks before ovulation and fertilization. Pregnancy: Diagnosis, Physiology, and Care
    • IVIG IVIG Dermatomyositis is NOT utilized, because there is a lack of data.
    • Delivery of hydropic children is considered a high risk.

Prevention[14,15]

  • General infection-control practices
  • High-risk individuals should be informed of measures to avoid exposure and when to seek medical attention Attention Focusing on certain aspects of current experience to the exclusion of others. It is the act of heeding or taking notice or concentrating. Psychiatric Assessment.

Differential Diagnosis

  • Hydrops Hydrops Cholecystitis fetalis: serious fetal condition that involves an accumulation of fluid in 2 or more fetal compartments including ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites, pleural effusion Pleural Effusion Pleural effusion refers to the accumulation of fluid between the layers of the parietal and visceral pleura. Common causes of this condition include infection, malignancy, autoimmune disorders, or volume overload. Clinical manifestations include chest pain, cough, and dyspnea. Pleural Effusion, pericardial effusion Pericardial effusion Fluid accumulation within the pericardium. Serous effusions are associated with pericardial diseases. Hemopericardium is associated with trauma. Lipid-containing effusion (chylopericardium) results from leakage of thoracic duct. Severe cases can lead to cardiac tamponade. Pericardial Effusion and Cardiac Tamponade, and skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema. The condition carries a poor prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas for perinatal survival.
  • Aplastic crisis: occurs with significantly reduced production of RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology resulting in a rapid decline in the hemoglobin level with reticulocytopenia. With parvovirus B19 Parvovirus B19 Primate erythroparvovirus 1 (generally referred to as parvovirus B19, B19 virus, or sometimes erythrovirus B19) ranks among the smallest DNA viruses. Parvovirus B19 is of the family Parvoviridae and genus Erythrovirus. In immunocompetent humans, parvovirus B19 classically results in erythema infectiosum (5th disease) or “slapped cheek syndrome.” Parvovirus B19 infection, the marrow function generally returns spontaneously within 1 week.
  • Arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis: joint disorder characterized by joint pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and stiffness accompanied by other manifestations such as redness Redness Inflammation, warmth, swelling Swelling Inflammation, and decreased range of motion Range of motion The distance and direction to which a bone joint can be extended. Range of motion is a function of the condition of the joints, muscles, and connective tissues involved. Joint flexibility can be improved through appropriate muscle strength exercises. Examination of the Upper Limbs in joints.
Table: Comparison of common childhood rashes Rashes Rashes are a group of diseases that cause abnormal coloration and texture to the skin. The etiologies are numerous but can include irritation, allergens, infections, or inflammatory conditions. Rashes that present in only 1 area of the body are called localized rashes. Generalized rashes occur diffusely throughout the body. Generalized and Localized Rashes
Number Other names for the disease Etiology Description
1st disease 1st disease Measles (also known as rubeola) is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. It is highly contagious and spreads by respiratory droplets or direct-contact transmission from an infected person. Typically a disease of childhood, measles classically starts with cough, coryza, and conjunctivitis, followed by a maculopapular rash. Measles Virus
  • Measles Measles Measles (also known as rubeola) is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. It is highly contagious and spreads by respiratory droplets or direct-contact transmission from an infected person. Typically a disease of childhood, measles classically starts with cough, coryza, and conjunctivitis, followed by a maculopapular rash. Measles Virus
  • Rubeola Rubeola Measles (also known as rubeola) is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. It is highly contagious and spreads by respiratory droplets or direct-contact transmission from an infected person. Typically a disease of childhood, measles classically starts with cough, coryza, and conjunctivitis, followed by a maculopapular rash. Measles Virus
  • 14-day measles 14-day measles Measles (also known as rubeola) is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. It is highly contagious and spreads by respiratory droplets or direct-contact transmission from an infected person. Typically a disease of childhood, measles classically starts with cough, coryza, and conjunctivitis, followed by a maculopapular rash. Measles Virus
  • Morbilli Morbilli Measles (also known as rubeola) is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. It is highly contagious and spreads by respiratory droplets or direct-contact transmission from an infected person. Typically a disease of childhood, measles classically starts with cough, coryza, and conjunctivitis, followed by a maculopapular rash. Measles Virus
Measles Measles Measles (also known as rubeola) is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. It is highly contagious and spreads by respiratory droplets or direct-contact transmission from an infected person. Typically a disease of childhood, measles classically starts with cough, coryza, and conjunctivitis, followed by a maculopapular rash. Measles Virus morbillivirus Morbillivirus A genus of the family paramyxoviridae (subfamily paramyxovirinae) where the virions of most members have hemagglutinin but not neuraminidase activity. All members produce both cytoplasmic and intranuclear inclusion bodies. Measles virus is the type species. Measles Virus
  • Cough, coryza Coryza Inflammation of the nasal mucosa, the mucous membrane lining the nasal cavities. Rhinitis, conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis
  • Koplik’s spots (blue-white spots with a red halo) on the buccal membrane
  • Maculopapular Maculopapular Dermatologic Examination rash Rash Rocky Mountain Spotted Fever begins on the face and behind the ears → spreads to trunk/extremities
2nd disease
  • Scarlet fever Scarlet fever Infection with group a Streptococci that is characterized by tonsillitis and pharyngitis. An erythematous rash is commonly present. Scarlet Fever
  • Scarlatina Scarlatina Infection with group a Streptococci that is characterized by tonsillitis and pharyngitis. An erythematous rash is commonly present. Scarlet Fever
Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus pyogenes
3rd disease 3rd disease An acute infectious disease caused by the rubella virus. The virus enters the respiratory tract via airborne droplet and spreads to the lymphatic system. Rubella Virus
  • Rubella Rubella An acute infectious disease caused by the rubella virus. The virus enters the respiratory tract via airborne droplet and spreads to the lymphatic system. Rubella Virus
  • German measles German measles An acute infectious disease caused by the rubella virus. The virus enters the respiratory tract via airborne droplet and spreads to the lymphatic system. Rubella Virus
  • 3-day measles 3-day measles An acute infectious disease caused by the rubella virus. The virus enters the respiratory tract via airborne droplet and spreads to the lymphatic system. Rubella Virus
Rubella Rubella An acute infectious disease caused by the rubella virus. The virus enters the respiratory tract via airborne droplet and spreads to the lymphatic system. Rubella Virus virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology
  • Asymptomatic in 50% of cases
  • Fine macular rash Rash Rocky Mountain Spotted Fever on the face (behind the ears) → spreads to the neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess, trunk, and extremities (spares palms/soles)
  • Forscheimer spots: Pinpoint red macules and petechiae Petechiae Primary Skin Lesions can be seen over the soft palate Soft palate A movable fold suspended from the posterior border of the hard palate. The uvula hangs from the middle of the lower border. Palate: Anatomy/ uvula Uvula A fleshy extension at the back of the soft palate that hangs above the opening of the throat. Peritonsillar Abscess
  • Generalized tender lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy
4th disease
  • Staphylococcal Scalded Skin Syndrome Staphylococcal Scalded Skin Syndrome Staphylococcal scalded skin syndrome (SSSS), also known as Ritter disease and staphylococcal epidermal necrolysis, is a toxin-mediated condition caused by Staphylococcus aureus. The exfoliative toxin produced disseminates and cleaves desmoglein 1 in the epidermis, causing separation and detachment of the skin. Staphylococcal Scalded Skin Syndrome (SSSS)
  • Filatow-Dukes’ disease
  • Ritter’s disease
Due to Staphylococcus aureus Staphylococcus aureus Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications. Brain Abscess strains that make epidermolytic (exfoliative) toxin
  • Some believe that 4th disease is a misdiagnosis and, thus, nonexistent.
  • The term was dropped in the 1960s and is only used for medical trivia today.
  • Begins with a diffuse erythematous rash Rash Rocky Mountain Spotted Fever that usually begins around the mouth → fluid-filled bullae Bullae Erythema Multiforme or cutaneous blisters → rupture and desquamate
  • Nikolsky sign: Applying pressure on the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions with a finger (stroking) results in sloughing off of upper layers.
5th disease Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion infectiosum Erythrovirus or parvovirus B19 Parvovirus B19 Primate erythroparvovirus 1 (generally referred to as parvovirus B19, B19 virus, or sometimes erythrovirus B19) ranks among the smallest DNA viruses. Parvovirus B19 is of the family Parvoviridae and genus Erythrovirus. In immunocompetent humans, parvovirus B19 classically results in erythema infectiosum (5th disease) or “slapped cheek syndrome.” Parvovirus B19 (Primate erythroparvovirus Erythroparvovirus Parvovirus B19 1)
  • Facial erythema (“slapped-cheek rash”) that consist of red papules on the cheeks Cheeks The part of the face that is below the eye and to the side of the nose and mouth. Melasma
  • Begins on the face → spreads to the extremities → extends to trunk/buttocks
  • Initially confluent, then becomes net-like or reticular as it clears
6th disease
  • Exanthem Exanthem Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke’s disease), fifth (erythema infectiosum), and sixth (exanthema subitum) numeric designations survive as occasional synonyms in current terminology. Varicella-Zoster Virus/Chickenpox subitum
  • Roseola infantum Roseola infantum An acute, short-lived, viral disease of infants and young children characterized by a high fever at onset that drops to normal after 3-4 days and the concomitant appearance of a macular or maculopapular rash that appears first on the trunk and then spreads to other areas. It is the sixth of the classical exanthematous diseases and is caused by HHV-6. Human Herpesvirus 6 and 7
  • Rose rash Rash Rocky Mountain Spotted Fever of infants
  • 3-day fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
Human herpesvirus 6B or human herpesvirus 7
  • Sudden onset of high fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
  • Nagayama spots: papular spots on the soft palate Soft palate A movable fold suspended from the posterior border of the hard palate. The uvula hangs from the middle of the lower border. Palate: Anatomy/ uvula Uvula A fleshy extension at the back of the soft palate that hangs above the opening of the throat. Peritonsillar Abscess
  • Rash Rash Rocky Mountain Spotted Fever begins as fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever resolves (the term “ exanthem Exanthem Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke’s disease), fifth (erythema infectiosum), and sixth (exanthema subitum) numeric designations survive as occasional synonyms in current terminology. Varicella-Zoster Virus/Chickenpox subitum” describes “surprise” of rash Rash Rocky Mountain Spotted Fever after the fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever subsides)
  • Numerous rose-pink, almond-shaped macules on the trunk and neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess → sometimes spreads to face/extremities

References

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