LCH is marked by the clonal proliferation of Langerhans cells—specialized dendritic cells of the myeloid lineage—resulting in distinct clinical manifestations, with an estimated incidence of five cases per million children[17–19]. Although it predominantly affects children aged 1–3, LCH can occur at any age, with cases documented across a broad age range. In a cohort of 315 pediatric patients, 173 (55%) harbored the BRAF V600E mutation, known to be associated with a more aggressive disease course and poorer prognosis[15]. The susceptibility of LCH patients to PJP is heightened by direct disruption of immune regulation by the disease and by immune suppression, particularly from therapies like vinblastine and corticosteroids[20–21]. Standard treatments for LCH include specific chemotherapeutic agents such as vinblastine and corticosteroids, along with adjunctive radiotherapy in refractory cases[22]. While effective in controlling LCH, these treatments weaken both cell-mediated and humoral immunity, increasing vulnerability to opportunistic infections such as PJP[23–24]. Additionally, the pulmonary involvement in LCH can predispose to severe manifestations of PJP, often presenting with more intense inflammation and hypoxemia than typically observed in HIV-related cases[19, 25]. PJP is a life-threatening opportunistic infection prevalent among individuals with compromised immune systems, including those undergoing chemotherapy for cancer, patients with autoimmune diseases, and those with a range of congenital or acquired immunodeficiencies[26]. Clinically, PJP presents with exertional dyspnea, fever, and chest pain. It progresses rapidly, often leading to severe hypoxemia and a high mortality rate. A retrospective study of 30 non-HIV patients with PCP and respiratory failure showed a mortality rate of 67%, rising to 100% if severe ARDS, pneumothorax, or other complications occurred[27]. Despite aggressive pharmacotherapy and mechanical ventilation in the PICU, this patient's condition deteriorated, marked by worsening respiratory distress and severe respiratory acidosis unresponsive to conventional treatments, ultimately requiring ECMO support.
ECMO, a sophisticated life-support technology, is typically used as a temporary intervention for patients experiencing severe respiratory or cardiac failure unresponsive to conventional treatments. By partially or completely substituting for cardiopulmonary functions, ECMO ensures tissue oxygenation while allowing diseased heart and lung tissues to rest, thereby buying time for recovery. Recent applications of ECMO have shown success in managing complex conditions such as pulmonary hypertension, facilitating postoperative recovery in lung transplantations, treating bronchopleural fistulas, and supporting severe respiratory distress in COVID-19 cases[28–31]. Pediatric success rates for ECMO, particularly in cases of severe respiratory failure, typically range from 20%-40%, reflecting variations in underlying conditions and severity[32–33]. Notably, a recent prospective cohort study highlighted an impressive 89% survival rate among pediatric patients with PJP managed with ECMO, underscoring its potential life-saving role in severe cases[34]. The two predominant ECMO modalities are veno-venous (V-V) ECMO for respiratory failure and V-A ECMO for circulatory failure. In the V-V ECMO, blood is extracted from venous sites, oxygenated externally through a membrane lung, and then returned to the venous system, utilizing either the original extraction point or a different venous site for re-entry. This mode relies on the patient's heart to recirculate oxygenated blood, initially achieving arterial saturations of only 75%-85%. This improves as native lung function recuperates. Hypotension is a common complication with V-V ECMO, often resulting from decreased cardiac filling pressures as venous blood is diverted into the ECMO circuit, which may necessitate adjustments in fluid management or vasopressor support[31]. Conversely, V-A ECMO, ideal for cases involving both cardiac and respiratory failure, extracts blood from the right atrium or a central vein, performs oxygenation and carbon dioxide removal, and returns it to the arterial system, thus ensuring both systemic oxygenation and circulatory support. This modality achieves a higher proportion of oxygenated blood compared to native arterial blood, which is critical in maintaining normal arterial oxygen saturations and supporting vital organ function in severe respiratory and cardiac failure[35]. V-A ECMO aims to mechanically support circulation while providing oxygenation and carbon dioxide removal as needed, allowing simultaneous respiratory and circulatory support and mitigating the effects of severe lung damage that could lead to cardiac enlargement, pulmonary hypertension, and refractory heart failure[35–36]. In this case report, the patient initially presented with respiratory acidosis and a persistent decline in the oxygenation index, indicative of severe respiratory failure. Concurrently, significant lactic acidosis suggested substantial tissue hypoperfusion. The need for high-dose vasopressors to maintain circulation and cardiac output demonstrated hemodynamic instability. These factors provided a factual basis for the use of V-A ECMO in this patient.
In our systematic review, we identified six immunocompromised patients with severe Pneumocystis jirovecii pneumonia who were treated using ECMO with a V-V configuration, encompassing all cases that satisfied our inclusion criteria. Among these, five patients survived, with ECMO support durations ranging from 18 to 72 days and a median of 45 days. In the fatal case, the patient was weaned off V-V ECMO after 17 days. Subsequent to ECMO decannulation, this patient exhibited progressive pulmonary inflammation and experienced seizures of indeterminate origin, both of which culminated in mortality. In contrast, the pediatric patient described in our report was treated using V-A ECMO, and ECMO support was successfully discontinued after only 14 days, which is notably shorter than the average duration reported in previous cases. Importantly, this notable outcome was achieved without any adverse complications such as intensive care unit-acquired weakness, catheter-related bloodstream infections, or ischemic-hypoxic encephalopathy, underscoring the efficacy and safety of this therapeutic approach. The V-A ECMO configuration, as suggested by emerging research and our observations, may offer distinct advantages in managing ARDS induced by PJP in immunocompromised pediatric patients, particularly in improving hemodynamic support alongside respiratory function. The V-A mode is often preferred for younger children due to its less reliance on large-caliber vein availability, which is a challenge in small patients, and its ability to provide both respiratory and cardiovascular support even with limited vascular access. In this case, the patient was treated using a neck-based arteriovenous ECMO setup, chosen for its rapid accessibility and reduced complications associated with lower body catheterization, effectively overcoming the typical challenges of V-V setups in small patients and achieving successful treatment. Blood return in this setup is generally facilitated through side grafts near the aortic arch, which minimizes differential oxygenation—a condition where different parts of the body receive blood with varying oxygen levels[37]. Currently, in pediatric ECMO protocols requiring cervical vessel cannulation, the standard management involves unilateral ligation of the carotid and jugular vessels, which blocks blood flow and may risk sequential neurological damage, including cerebral atrophy and focal seizures[38]. In this case, a novel approach was taken by performing arteriovenous anastomosis on the right cervical vessels post-ECMO, aimed at mitigating neurodevelopmental sequelae such as epilepsy, commonly associated with unilateral ligation. This unique intervention, unreported in previous cases, was tailored to the patient’s anatomical and risk profiles.
This case report is subject to certain limitations. Firstly, the generalizability of our findings may be limited due to the involvement of a single patient with specific clinical and demographic characteristics, such as age and underlying conditions. The uniqueness of this case, particularly the coexistence of Langerhans Cell Histiocytosis with severe pneumocystis jirovecii pneumonia, implies that our findings might not be directly applicable to all patients with either condition separately. Moreover, despite an exhaustive review, the existing literature provides limited clinical data on the progression and optimal treatment responses for PJ infections in immunocompromised children, hindering a comprehensive understanding. Additionally, while ECMO was effective in this instance, the absence of randomized controlled trials focusing on this patient subgroup limits the ability to validate its efficacy and safety universally. Future studies should thus aim to design clinical trials with control groups to ascertain the effectiveness and safety of ECMO in treating such patients. Lastly, the lack of specialized guidelines for treating severe PJP in patients with LCH increases treatment decision-making uncertainty, underscoring the need for targeted research that can inform future guideline development.