[CIS-PAGID] nontypeable haemophilus influenzae and panniculitis in 14 day old female

[Larkin, Allyson]

Dear Colleagues,

I am requesting help regarding a 14 day old female with nontypeable haemophilus influenzae bacteremia, meningitis and skin lesions that show acute neutrophil rich necrotizing panniculitis.



History: First baby to non cansanguinous parents. Full term pregnancy. Mother on methadone. Forceps delivery for fetal  bradycardia. Low Apgars at birth. Went to NICU with neutropenia, tachypnea, abdominal distension and poor feeding. Blood cultures grew nontypeable H.Flu. CSF consistent with meningitis.  Clinical status improved with antibiotics, off vent, feeding but infant developed large, soft masses on neck and lower back (2.1x0.9x2.4cm and 1.7x0.7x2.6 cm). Bx showed neutrophil rich necrotizing panniculitis. Drained but sterile. Umbilical cord has separated with no complications.



Labs/Studies:

·        Admission CBC: WBC 2.1, Hgb 14, Hct 39, Plts 39, abs neuts 1030, abs lymphs 420 (she than had multiple plt transfusions)

·        Most recent CBC: WBC 14, Hgb 13, Hct 38.5, plts 255, Abs neuts 6920, abs lymphs 4750

·        IgA 22, IgG 625, IgM 135

·        HIV antibody screen negative

·        Skin Bx: extensive necrosis of the panniculus with diffuse neutrophilicinfiltrate.  The keratinizing squamous epithelium is does not show parakeratosis, acanthosis, or spongiosis.  The superficial dermis and adnexalstructures are largely uninvolved. The deeper reticular dermis shows marginating neutrophils with a neutrophilic exudate around the vessels with a diffuse neutrophilic infiltrate in the subcutaneous tissue.  This neutrophil-rich inflammatory infiltrate has associated basophilic necrosis. The sheets of neutrophils and necrosis are the predominant feature with no restriction of the inflammatory process to any compartment of the panniculus. Macrophages are not a predominant feature. No significant crystallization of the fat. There is no evidence of immature leukemic blasts. Gram stain negative. Grocott and PAS are negative for fungi. Fite stain is negative for Nocardia.

·        NOBA: Peripheral blood was evaluated for neutrophil oxidative burst activity in the presence and absence of phorbol myristate acetate (PMA), a stimulator of protein kinase C. This study demonstrates neutrophil oxidative burst activity with a normal stimulation index, but also shows slight pre-activation of the cells. These findings do NOT suggest chronic granulomatous disease.

·        Subsets:

    % T-Cells (CD3) 61 ( Ref. Range 58 - 64)
                                            Total T-Cells (CD3) 3,400 (Ref. Range 2,400 - 3,300)
                                            % Helper Cells (CD4) 49 (Ref. Range 36 - 50)
                                            Total Helper Cells (CD4) 2,761 (Ref. Range 1,600 - 2,200)
                                            % Suppressor Cells (CD8) 11 (Ref. Range 20 - 30)
                                            Total Suppressor Cells (CD8) 635 (Ref. Range 820 - 1,600)
                                            % B-Cells (CD19) 28 (Ref. Range 22 - 29)
                                            Total B-Cells (CD19) 1,593 (Ref. Range 1,000 - 1,600)
                                            % NK Cells (CD16/CD56) 7 (Ref. Range 7 - 21)
                                            Total NK Cells (CD16/CD56) n 372 (Ref. Range 270 - 1,100)
                                          Helper/Suppressor Ratio 4.35 (Ref. Range 1.70 - 3.10)

  *   Abdominal ultrasound: normal liver, spleen
 Assessment:

  *   I am concerned about a phagocytic disorder. I am thinking of neutrophil specific granule deficiency. Her peripheral blood smear looked suspicious to me for bilobed nuclei in the neutrophils (awaiting heme path review).
  *   I was hoping there might be suggestions/thoughts about other specific primary immunodeficiencies that might fit her clinical description.  Additionally, I was wondering if anyone had suggestions about further workup:
1) Performing electron microscopy to look at number of specific granules
2) Look at the granule proteins by Elisa
3) Look for mutation in CEBPE
4) Is there a role for bone marrow biopsy?
5) Is there a role for prophylactic antibiotics during this workup?

Thank you kindly for your thoughts,

Allyson Larkin, MD
Assistant Professor of Pediatrics
Department of Pulmonary Medicine, Allergy and Immunology
Children’s Hospital of Pittsburgh
One Children’s Hospital Drive
4402 Penn Avenue
Pittsburgh, PA 15224

Phone: 412-692-8903
Fax: 412-692-8499
E-mail: allyson.larkin at chp.edu