|Year : 2020 | Volume
| Issue : 4 | Page : 286-288
Pancytopenia with atypical skin manifestation in a term newborn
Tapas Bandyopadhyay, Ranjani Upadhyay, Arti Maria
Department of Neonatology, PGIMER and Dr. RML Hospital, New Delhi, India
|Date of Submission||08-Oct-2019|
|Date of Decision||11-Jul-2020|
|Date of Acceptance||09-Aug-2020|
|Date of Web Publication||01-Oct-2020|
Prof. Arti Maria
PGIMER and Dr. RML Hospital, New Delhi
Source of Support: None, Conflict of Interest: None
Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder in neonates characterized by hyperinflammation along with abnormal proliferation and accumulation of mononuclear cells within various tissues due to pathologic immune activation. Cutaneous manifestations in HLH are rare and have been reported between 6% and 65% of the cases in the literature. We describe the case of a term newborn with HLH and atypical skin manifestations. The baby was diagnosed as a case of primary HLH according to HLH-2004 guidelines based on typical clinical and laboratory findings. No specific genetic defect was identified. Subsequently, during hospital stay, the baby developed atypical skin lesions suggestive of “Noma Neonatorum.” He was managed aggressively with antibiotics as per the culture sensitivity report. However, the baby succumbed to rapidly progressive HLH. This is the first case report we are aware of “Noma Neonatorum” occurring in an infant with HLH. Although the cutaneous manifestations are not common, “Noma Neonatorum” should be kept in mind as an accompanying condition in neonates with HLH.
Keywords: Hemophagocytic lymphohistiocytosis, newborn, noma neonatorum, pancytopenia, primary
|How to cite this article:|
Bandyopadhyay T, Upadhyay R, Maria A. Pancytopenia with atypical skin manifestation in a term newborn. J Clin Neonatol 2020;9:286-8
| Case Details|| |
A 38 + 0 weeks old baby boy born out of 1st order consanguineous marriage to a 33-year-old P1A1 mother by cesarean section due to intrapartum fetal distress through clear amniotic fluid. The baby required resuscitation at birth. On 2nd day of life, the baby started having fever accompanied by hepatosplenomegaly, anemia (11 g/dl), leukopenia (2600/mm3), and thrombocytopenia (20,000/mm3) for which he received intravenous antibiotics and blood components transfusion as per the unit protocol. Subsequently, the baby received multiple blood component transfusions before admission to our hospital.
The baby was brought to our neonatal intensive care unit (NICU) on 22nd day of life due to lack of clinical improvement. At admission to NICU, baby was pale, hypotonic, febrile and was having respiratory distress. Systemic examination revealed massive hepatosplenomgaly with petechial spots all over the trunk. The laboratory findings were as follows: hemoglobin 5.3 g/dl, white blood cell 1200/mm3 (neutrophils 84%), platelets 60,000/mm3, reticulocytes 2.0%, and C-reactive protein 30 mg/L. Blood cultures was sterile. Baby was managed with blood component transfusion, broad spectrum antibiotics along with supportive care. Although there was slight clinical improvement after admission, on day 32 of life, the baby developed multiple episodes of fever with deteriorating respiratory status. Baby also developed multiple ulcerative necrotic lesion over the face initially which progressed rapidly to involve neck, trunk, and scrotum suggestive of “Noma Neonatorum” [Figure 1]. Repeat investigations showed persistence of pancytopenia. Both blood culture as well as cultures taken by swabbing the lesions had grown pseudomonas. The condition was managed with appropriate antibiotics as per the sensitivity report. New lesions continue to crop during the next 1 week. After ruling out bacterial sepsis and common viral causes of bone marrow suppression investigations in line of hemophagocytic lymphohistiocytosis (HLH) was planned which showed serum ferritin values of >1000 ng/ml, fibrinogen level was 116 mg/dl, and triglyceride levels 256 mg/dl. Bone marrow biopsy showed many histiocytes (CD68+) with hemophagocytosis. Hence, a diagnosis of HLH was established, pending genetic mutation report with a plan to start on induction chemotherapy according to the HLH 2004 chemotherapy protocol. The clinical condition of the baby continued to deteriorate further during 45th day of life with circulatory insufficiency and escalation of ventilator settings. Chest X-ray showed features of acute respiratory distress syndrome. Baby died on 50th day of life due to multiorgan dysfunction, septic shock, and disseminated intravascular coagulation.
|Figure 1: Necrotic skin lesions over nose and upper lips suggestive of noma neonatorum|
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| Discussion|| |
HLH is a hyperinflammatory syndrome known as histiocytosis, which is characterized by an overabundance of tissue macrophages or histiocytes due to pathologic immune activation. The exact incidence of this condition is unknown and may range from 1 in 50,000 to 150,000. This entity could be either familial or sporadic, which can be difficult to differentiate at the time of presentation. The familial or primary HLH cases usually has autosomal recessive or X-linked inheritance based on whether the genetic mutation occurred within the familial HLH loci or in a genetic loci responsible for an immune deficiency.
The final pathophysiological events in both familial or sporadic cases includes continued activation of cytotoxic T-cell and natural killer (NK) cell signaling pathways, resulting in the continual production of cytokines and activation of macrophages. Subsequent accumulation of lymphohistiocytosis in many organs leads to the appearance of signs and symptoms.
Mutations at the fHLH2 loci within the perforin gene (PRF1) on chromosomes 10q22.1 has been shown in 20%–40% of the familial HLH cases. The other genes involved in the pathogenesis includes Munc18-2, Munc13-4, and the syntaxin 11 gene.
The 2004 HLH diagnostic criteria includes either a molecular diagnosis consistent with primary HLH or the presence of at least 5 of the 8 essential criteria, i.e., persistent fever, splenomegaly, cytopenias of two or three lineages (unassociated with a hypocellular or dysplastic marrow), hypertriglyceridemia and/or hypofibrinogenemia, ferritin ≥500 ng/ml, sCD25 ≥2400 U/ml, decrease/absence of NK cell activity, and histopathological evidence of hemophagocytosis in the bone marrow, spleen, liver, or lymph nodes. The early severe manifestation of the illness satisfying both the clinical and laboratory diagnostic criteria of HLH and associated adverse outcome in the index case are highly suggestive of primary form of HLH. The molecular diagnosis was not possible, both due to the lack of such facility at our center as well as lack of infrastructure to get it done from private laboratory.
Noma neonatorum is a rare gangrenous disorder, which during its course, causes progressive mutilating destruction of the soft tissues and the bone. The condition was first described in 1977 in 48 preterm neonates. Majority of them having disease onset after 3rd day of life and succumbed within first 3 days after the disease onset. Although the exact pathogenesis of the disease is still unknown, it is postulated that infection may be the inciting factor in the causation of this entity combined with both generalized and local circulatory inadequacy and poorly developed immune system. Noma Neonatorum is relatively rare in term infants although few case reports in full-term babies have also been described. The skin manifestations [Figure 1] in the index case are typically consistent with the diagnosis of noma neonatorum.
To the best of our knowledge, the association of HLH with noma neonatorum has not been reported in the literature till date.
The main objectives of treatment in HLH include suppression of cytokine storm, inflammatory response, and immune dysregulation. The HLH 2004 protocol includes use of Etoposide, Cyclosporine A, and Corticosteroids. Emapalumab is the first Food and Drug Administration-approved drug for HLH, specifically for the treatment of adult and pediatric patients with primary HLH that is refractory, recurrent, progressive, or intolerant to conventional therapy but not as of now recommended for its use in neonates. Allogenic bone marrow transplantation currently remains the treatment of choice in primary cases.
The management of noma neonatorum includes initial use of broad spectrum antibiotics and subsequently can be modified as per the sensitivity pattern of the isolated organism along with supportive care.
To conclude, HLH is extremely rare in neonates. Clinicians should consider this entity in their differentials in any neonate presenting with an early history of unexplained fever, hepatosplenomegaly, and pancytopenia. The association of noma neonatorum with HLH is extremely rare and must be managed aggressively due to high incidence of mortality. Whenever possible genetic testing should be considered if there is a clinical suspicion of HLH.
Declaration of patient consent
The authors declare that they have obtained appropriate patient consent from the baby's father for their images and other clinical information to be reported in the journal. The attendant understand that their names and initials will not be published and due effort will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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