The diversity of clinical manifestations of human monkeypox should be emphasized in practice.

Abstract

The World Health Organization (WHO) announced on July 23, 2022, that the human monkeypox (HMPX) epidemic 2022 was a public health emergency of international concern. In the current outbreak, the main HMPX patients were men who had sex with men in adults. Children less than 18 years of age accounted for only 0.15% (27/17 641) of the confirmed HMPX cases in this outbreak.1 However, children were absolutely the main victims of HMPX in previous investigations. Among HMPX cases, 93% were children under 15 years of age while the age group of children 3-4 years had the highest proportion (27%) of cases, followed by those aged 5–6 years (20%) and those 1–2 years old (19%).2 As HMPX continues to spread across the U.S. in 2022, the number of children infected with the virus is growing as well since this July. The U.S. Centers for Disease Control and Prevention (CDC) reported at least 17 confirmed and probable HMPX cases among children aged 15 and younger, in whom some were tested positive at school.3 The pediatricians should prepare actively to deal with HMPX. The clinical manifestations of HMPX in children were proved to be similar to those of infections in adults.4 Typically, the prodromal stage of HMPX is characterized by fever, fatigue, muscle pain, headache, back pain, and other systemic symptoms, accompanied by local or systemic lymphadenopathy; 1–3 days after the disease onset, the patient develops a rash, which often spreads from the face to other parts of the body, and may involve the palms and soles; the rash goes through the stages of macules, papules, vesicles in 3–6 days and to pustules for 5–7 days. Then the pustules experience umbilication, drying, and desquamating within the following 7–14 days.4 WHO interprets the typically described clinical picture for monkeypox with fever, and swollen lymph nodes, followed by centrifugal rashes.5 However, a variety of different and complex clinical manifestations were recorded in previous and current HMPX outbreaks. The diversity of the clinical charicteristics should be recognized by clinicians in practice. Back pain was not a common symptom in the U.S. HMPX outbreak in 2003, in which hemorrhagic pustules were first recorded.6 In the outbreak in Nigeria from 2017 to 2018, the scalp was also frequently affected by the lesions in the patients, and the fever occurred after the rash in 43% of the cases with fever.7 Atypical manifestations in the current HMPX cases included the presentation of only a few or just a single lesion, absence of skin lesions in some cases, anal pain and bleeding, lesions in the genital or perineal/perianal area which do not spread further, lesions appearing at different (asynchronous) stages of development, and the appearance of lesions before the onset of fever, malaise and other constitutional symptoms (absence of prodromal period).5 In fact, the time relationship between rash, lymph node enlargement, fever, headache, myalgia, and other systemic clinical manifestations in HMPX cases, as well as the course evolution of specific symptoms and signs, may change, showing characteristics different from those usually described. Atypical features such as no rash, no prodromal symptoms, rash before the fever, and only a local single lesion, and even asymptomatic infections have already been reported.1, 8 Several factors have been identified that may affect the clinical manifestation of HMPX. It is well known that the genetic background of monkeypox virus (MPXV) is obviously related to the severity and mortality of HMPX and that vaccinia immunization leads to mild clinical manifestations with less rash and lower occurrence of complications.4 The route of MPXV infection was proved to influence the clinical manifestations of HMPX; e.g. the patients who had complex exposure type associated with bite or scratch by infected animals presented different symptoms and signs as compared to the cases with non-invasive exposure type.9 Co-infection may also affect the clinical manifestation of HMPX. The HMPX cases, co-infected with varicella zoster virus or HIV, presented different characteristics as compared to those with a single MPXV infection.10, 11 In the early stage of the HMPX epidemic in 2022, 109 cases (29%) were found to be complicated with other sexually transmitted diseases (STD), including gonorrhea (8%), chlamydia infection (5%), and syphilis (9%).8 In addition, HMPX can have a series of complications, which undoubtedly increase the complexity of clinical manifestations. Therefore, clinicians, including pediatricians, must be aware that the clinical manifestations of HMPX are complex and various. Because of the diverisity of the first and prominent manifestations, patients will visit any departments besides the department of infectious disease, dermatology, or STD clinic. All clinical departments could become the first visit place of HMPX cases in the general hospitals, as well as the children's hospitals. None.