An “atypical exanthem” (AE) is a rash that differs in morphology and etiology from classic exanthems such as measles, scarlet fever, rubella, erythema infectiosum, roseola, and varicella (1, 2). The sudden onset and often extensive cutaneous involvement of AEs often prompts urgent medical evaluation. The clinical presentation of AEs is variable, ranging from mild and self-limiting to severe, life-threatening conditions that require prompt recognition and treatment. Although viral infections are the most common underlying cause, followed by drug reactions and, less frequently, bacterial or parasitic infections, determining the specific etiology remains challenging, particularly when multiple potential triggers coexist (1, 2). Pediatric oncology patients, especially those undergoing immunosuppressive therapies such as chemotherapy or hematopoietic stem cell transplantation (HSCT), are highly susceptible to atypical exanthems (3). Their immunosuppressed state complicates diagnosis, as AEs may mimic infections, drug reactions, or graft-versus-host disease (GvHD), each of which requires different management strategies (4). In this context, timely and accurate diagnosis is essential not only for optimizing patient management but also for guiding infection control and public health strategies (5). While community-acquired respiratory viruses (CARVs) such as rhinovirus and respiratory syncytial virus (RSV) are common in pediatric patients, their association with cutaneous manifestations remains poorly characterized.

We present a case series of atypical viral exanthems associated with CARVs in pediatric oncohematology patients, highlighting diagnostic challenges and outcomes. Participation in the study was voluntary, and appropriate informed consent was obtained in accordance with ethical guidelines, including those of the Declaration of Helsinki.

At our tertiary care center, pediatric oncology patients are regularly referred to dermatology for evaluation of atypical cutaneous eruptions. We report four such cases, all characterized by self-limiting, nonpruritic or mildly pruritic erythematous-papular eruptions in the setting of impaired immune function. The rashes predominantly involved the trunk and extremities, were associated with low-grade fever, had no mucosal involvement, and resolved within a few days without deterioration in general health or significant changes in systemic therapy. In each case, molecular diagnostics identified a community-acquired respiratory virus—rhinovirus or RSV—as the likely etiologic agent, with viral clearance confirmed in follow-up testing.

All patients underwent a standardized diagnostic workup that included a thorough clinical history, physical examination, and laboratory testing. This included complete blood counts, inflammatory markers, and microbiology studies in accordance with institutional protocols for immunosuppressed pediatric patients. These included anti-streptolysin O titers and IgG/IgM serologies for pathogens such as Mycoplasma pneumoniae, Epstein–Barr virus (EBV), cytomegalovirus (CMV), varicella-zoster virus (VZV), HIV, parvovirus B19, and coxsackievirus. Real-time quantitative PCR was also performed on blood and/or nasopharyngeal swabs to detect viral DNA or RNA, including CMV, EBV, HHV-6 and -7, parvovirus B19, coxsackievirus, and, based on clinical suspicion, community-acquired respiratory viruses such as rhinovirus and RSV. A viral etiology was confirmed when the pathogen was identified in the acute phase, cleared in the convalescent phase, and no alternative cause was found.

AE are common in pediatric patients and often have a viral etiology (1, 2). However, in immunocompromised children, such as those undergoing chemotherapy or hematopoietic stem cell transplantation (HSCT), these rashes pose significant diagnostic challenges due to their broad differential diagnosis, including drug reactions, graft-versus-host disease (GvHD), or manifestations of the underlying disease.

Advances in therapies such as chemotherapy, radiation and BMT have improved outcomes but also increased the risk of complications, particularly infections, in this population (7, 8). Immunosuppression, whether disease-related or therapy-induced, profoundly impairs host defense mechanisms, increasing susceptibility to infections and complicating their diagnosis (4, 9).

Viral infections, which are usually mild and self-limiting in healthy children, can cause substantial morbidity and mortality in immunocompromised patients (8, 9). CARVs, including rhinovirus and RSV, are common in this group (10, 11) and unlike other pathogens such as HSV, VZV and CMV, no effective prophylaxis currently exists, leaving these viruses as a persistent threat (11).

While CARVs typically cause respiratory disease, their potential to present with isolated dermatologic manifestations remains underrecognized. Rhinovirus, traditionally associated with upper respiratory tract infections in healthy individuals, emerged as the causative agent in two cases (12–14). Despite its established role in respiratory infections, rhinovirus-associated cutaneous manifestations remain sparsely reported (15, 16). The two cases herein provide further evidence of its potential to induce rashes in immunocompromised patients, even in the absence of respiratory symptoms.

RSV is a leading cause of acute lower respiratory tract infections worldwide, particularly in infants and young children, frequently resulting in hospitalization due to bronchiolitis and pneumonia (17, 18). Although predominantly linked to respiratory disease, extrapulmonary manifestations of RSV, including cardiovascular complications, seizures, hepatitis, and scarlatiniform eruptions involving the trunk and face, have been documented (19–21). In our series, RSV infection was associated with maculopapular rashes without significant systemic involvement in two cases. Notably, immunocompromised pediatric cancer patients may require interventions ranging from symptomatic management to intensive therapies, including oxygen supplementation and mechanical ventilation in severe respiratory cases (22).

In immunocompetent children, viral exanthems are typically diagnosed clinically in primary care settings, with laboratory confirmation rarely sought due to the self-limited nature of the disease and the low risk of complications. However, in immunocompromised hosts, even benign-appearing rashes may raise concern for serious disease, necessitating a more thorough diagnostic approach. Molecular diagnostics, particularly PCR testing of nasopharyngeal swabs, played a critical role in confirming viral etiology and guiding management decisions in our cases. Identification of viral RNA during acute illness and subsequent clearance at follow-up strengthened causal attribution and minimized unnecessary diagnostic procedures or therapeutic interventions. In particular, biopsies, while potentially informative, should be carefully considered in this patient population due to the inherent risks of infection and delayed wound healing associated with immunosuppression. However, clinicians should remain aware of the limitations of PCR, including differentiation of primary infections from reactivations.

Clinically, some features of these viral exanthems may help distinguish them from other causes (23–25). Recognition of a recurrent clinical pattern, such as a self-limiting, nonpruritic or mildly pruritic, erythematous-papular rash associated with low-grade fever involving the trunk and extremities and sparing the mucous membranes, may raise clinical suspicion of a viral etiology. Increased awareness of CARV-associated exanthems may allow clinicians to take a conservative, targeted approach, especially when close observation is possible. Dermatologic consultation can contribute significantly not only to accurate diagnosis, but also to resource rationalization and avoidance of unnecessary interventions-a strategy appreciated by patients’ families, who reported reassurance regarding the benign course of exanthems and the stability of ongoing treatments. In conclusion, the multifactorial nature of atypical exanthems in pediatric oncology underscores the importance of a comprehensive, multidisciplinary approach. Collaboration between dermatologists, infectious disease specialists, and oncologists ensures accurate diagnoses, minimizes unnecessary treatment adjustments, and avoids inappropriate therapies. Despite the inherent limitations of a small, retrospective case series, our observations highlight CARVs as potential dermatologic pathogens in immunocompromised pediatric populations. Increased awareness and timely molecular diagnosis may prevent unnecessary biopsies, empiric treatments, and diagnostic delays, thereby optimizing patient outcomes. CARVs should be actively considered in the differential diagnosis of benign exanthems in immunocompromised children, and awareness of their dermatologic presentation may improve patient care.