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A cold abscess remains a cold case: Multiple neonatal staphylococcal cold abscesses of the large folds

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By Warren R. Heymann, MD, FAAD
Jan. 17, 2024
Vol. 6, No. 3

Dr. Warren Heymann photo
Graduating residents will usually ask me for parting words of wisdom. If I had to choose one morsel of advice, it would be to read and study throughout their career. I still marvel at reports of entities that I may have encountered but did not recognize because I had never heard of them. There is ample truth in the adage “the eye sees what the mind knows.” This commentary will focus on “Multiple Neonatal Staphylococcal Cold Abscesses of the Large Folds” (MNSCA), a disorder unbeknownst to me until I failed the photoquiz of a case presented by Pegalajar García et al. (1)

Huber et al first described MNSCA in 3 immunocompetent neonates who “developed bilateral, fistulizing staphylococcal abscesses of the large folds, with very slight surrounding inflammation, and without general symptoms. The short duration and uncomplicated local evolution rule out the group of scrofulodermas (mycobacterial lymphadenitis).” The clinical presentation was strikingly similar in all cases, with lesions appearing between the tenth and twelfth day of life. Cultures from all 3 cases demonstrated methicillin-sensitive Staphylococcus aureus (MSSA) from the abscesses and all had an associated omphalitis. The bacteria recovered in the umbilicus were identical to those isolated from the skin abscesses in tested cases. The authors offered two hypotheses regarding the dissemination of infection — “either transitory bacteraemia quickly controlled by an immunocompetent host or by protecting maternal antibodies, or contamination per continuum through the skin in a child colonized by Staphyloccocci aureus.” (2) I view the latter as being more plausible.

Hubiche et al performed a retrospective study of 13 cases with MNSCA. None of the neonates were premature. The median age at onset of the abscess was 10 days. No patients had fever or cellulitis. Abscesses localized at the inferior area of large skin folds. Two children had omphalitis and one had an abscess of the right calf. Six children had abscesses in two or more anatomical localizations, with most patients (n = 8) having 2 or more abscesses. MSSA was the only pathogen recovered from the abscesses. None of the 6 S. aureus samples analyzed for gene toxins harbored the Panton–Valentine leukocidin (PVL) gene. Seven children had systemic antimicrobial therapy. Incision of the abscess was performed in 6 patients, and spontaneous drainage occurred in the remaining neonates. Seven patients were hospitalized and 6 were treated as outpatients. All cases had a favorable outcome within 1 week. Ten patients had a long-term follow-up with a median age of 5 years. None experienced recurrent infections or other clinical signs suggestive of immunodeficiency. The authors suggest that MNSCA may be due to S. aureus skin colonization of the folds, where occlusion results in an elevated pH, increased humidity, and increased temperature — all conditions favoring the growth of S. aureus.

Image for DWII of multiple neonatal staphylococcal cold abscesses of the large folds
Image courtesy of Franck Boralevi.

The report that caught my attention was an 11-day-old boy who presented with a 3-day history of multiple nodules in the inguinal and axillary folds. He was afebrile and appeared well. An omphalitis, which developed on day 3 of life, preceded the nodular eruption and resolved with topical mupirocin twice a day for one week. His mother had gestational diabetes, and delivery was uncomplicated at 39 weeks. Physical examination demonstrated 2 firm yellowish nodules with peripheral erythema in the left inguinal fold and a similar nodule above the right axilla. Histopathology revealed dermal neutrophilic infiltrates with a Gram stain demonstrating Gram-positive bacteria in clusters. A culture from a nodule grew MSSA. Immunoglobulin levels and lymphocyte subpopulation counts were normal. The lesions resolved after 7 days of cloxacillin with no recurrences during a 2-month follow-up. (1)

I become nervous with neonatal consultations, being petrified about missing important life-threatening diagnoses. It is reasonable to be concerned about immunodeficiency disorders when confronted with abscesses. For cold abscesses (an abscess that lacks intense inflammation), one might consider tuberculosis or fungal infections. The Hyper-IgE syndrome (Job syndrome, due to a mutation in the STAT3 gene in approximately 70% of cases) usually presents with atopic dermatitis, recurrent Staphylococcal infections, and recurrent pulmonary infections. (4) Interleukin-1 receptor-associated kinase-4 (IRAK4) deficiency is an autosomal recessive disorder due to variants in IRAK4 that impair Toll-like receptor signaling, resulting in recurrent non-invasive (skin cold abscesses) and invasive bacterial infections with Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa, with a mortality rate exceeding 40%. (1) Interestingly, IRAK4 is a molecule, similar to myeloid differentiation primary response gene 88 (MyD88), which mediates signal transduction from most Toll-like receptors, IL-1 receptor, and IL-18 receptor. The clinical manifestations of MyD88 deficiency are very similar to IRAK4 deficiency. (5)

As noted in all cases of MNSCA to date, neonates were systemically well, with a uniform rapid resolution of disease. What puzzles me is why cold abscesses appear in immunocompetent hosts. Think of the 5 cardinal signs of inflammation — redness (rubor), swelling (tumour), heat (calor; only applicable on the extremities), pain (dolor), and loss of function (functio laesa). The first 4 were named by Celsus in ancient Rome (30–38 B.C.) and the last by Galen (A.D 130–200). (6) Are these neonates transiently (and/or locally) immunosuppressed where they cannot mount an adequate immunologic response? Alternatively, could they be so immunologically efficient that mounting a usual inflammatory response to infection is not necessary to thwart the infection?

MNSCA appears to be a benign condition with an excellent prognosis. Pagalajar Garcia et al state “it is important to consider MNSCA in the differential diagnosis of multiple nodules located in skin folds of neonates and to recognize a neonatal infection that may be managed with a conservative approach, avoiding invasive procedures.” I agree with the sentiment, although I am not certain how the authors define “invasive procedures.” From my perspective, in the neonatal unit any abscess should be cultured (and incised if necessary).

Point to Remember: Healthy neonates presenting with cold abscesses in skin folds and growing methicillin-sensitive Staphylococcus aureus on culture may have “Multiple Neonatal Staphylococcal Cold Abscesses of the Large Folds.” With appropriate treatment, this benign disorder will not have any untoward sequelae.

Our expert’s viewpoint

Howard Pride, MD, FAAD

This is a thorough review of multiple neonatal cold abscesses of the skin folds, an entity that I have not previously (knowingly) encountered. It is striking that all patients had a good outcome, whether hospitalized or managed as an outpatient. Just the same, I have a profound respect for the potential severity of a Staphylococcus aureus infection and am not ready to abandon some deeply rooted principles of management. If there is an abscess, I always drain and culture. All reported cases have grown MSSA, but I would still treat empirically for MRSA while awaiting cultures. Topical mupirocin, including to the umbilical stump, is a very reasonable adjunct. The significant paradigm shift for me is the thought that there must be some underlying immunodeficiency to account for multiple cold abscesses, something that did not materialize in any of these cases. I will now feel comfortable with simple observation after treatment, forgoing extensive laboratory evaluation and genetic testing in a child who is otherwise well.  

  1. Pagalajar García MD, Ródenas Herranz T, Perez López I, Ramos Pleguezuelos FM, Ruiz Villaverde R. Asymptomatic nodules in body folds of a newborn. Pediatr Dermatol 2022; 39: 458-460.

  2. Huber F, Léauté-Labrèze C, Lina G, Sarlangue J, Taïeb A, Boralevi F. Multiple neonatal staphylococcal cold abscesses of the large folds. J Eur Acad Dermatol Venereol. 2006 Nov;20(10):1197-200. doi: 10.1111/j.1468-3083.2006.01738.x. PMID: 17062031.

  3. Hubiche T, Chiaverini C, Goujon E, Bourrat E, Bes M, Del Giudice P, Boralevi F; ‘Groupe de Recherche de la Société Française de Dermatologie Pédiatrique’. Multiple neonatal staphylococcal cold abscesses in large skin folds: a benign neonatal skin infection. J Eur Acad Dermatol Venereol. 2019 Mar;33(3):e125-e128. doi: 10.1111/jdv.15323. Epub 2018 Nov 25. PMID: 30388319.

  4. Hafsi W, Yarrarapu SNS. Job Syndrome. 2021 Aug 31. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–. PMID: 30247822.

  5. Takada H. Creating Awareness for Primary Immunodeficiencies in Japan. Front Immunol. 2021 Dec 13;12:803459. doi: 10.3389/fimmu.2021.803459. PMID: 34966393; PMCID: PMC8710485.

  6. Punchard NA, Whelan CJ, Adcock I. The Journal of Inflammation. J Inflamm (Lond). 2004 Sep 27;1(1):1. doi: 10.1186/1476-9255-1-1. PMID: 15813979; PMCID: PMC1074343.

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