March 2008

Fig.4

Fig.5

Fig.6

Fig.7

DIAGNOSIS: Langerhans Cells Histiocytosis, Congenital Self-Healing Histiocytosis/Congenital Self-Healing Reticulohistiocytosis/Hashimoto Pritzker Type

HISTOLOGY:
Perivascular and periadnexal aggregates of histiocytes in the mid to deep dermis (Figs.4,5).
Abundant pale eosinophilic cytoplasm of the histiocytes
Some nuclear grooving present.
CD1a, S-100 and CD68 positive (Figs.6,7).

DISCUSSION:
Langerhans Cell Histiocytosis (LCH) represents a group of diseases with infiltrates of clonal histiocytes in various organs. Congenital Self-Healing Histiocytosis (CSHH) is a variant of LCH that affects newborns or neonates; it is characterized by histiocytic infiltrates that are limited to the skin, and is generally spontaneously resolving within 3 months time. Typical lesions are red-brown painless papules, nodules, and vesicles that can occur anywhere on the body. Lesions can be single or multiple. Patients are generally otherwise healthy and have no systemic symptoms. (In the patient presented here the CSHH is not thought to be related to her bacteremia). Lesions generally heal with some slight hyperpigmentation.

The diagnosis of LCH can be confirmed with histopathology. There are aggregates of mononuclear cells in the dermis with abundant eosinophilic cytoplasm. There may be a characteristic groove in the nuclei of the histiocytes. The infiltrating cells typically stain positive with S-100 and CD1a, although this is not always the case. Under electron microscopy, Birbeck granules may be seen in the cytoplasm of the histiocytes. The histology of CSHH is not specific to this type of LCH. Other variants of LCH that may have multi-organ involvement can have the same histology of cutaneous lesions. So far, it has not been possible to identify immunohistochemical stains that differentiate cutaneous only LCH (CSHH) from systemic LCH.

Other variants of LCH include Letterer-Siwe Disease (LSD), Hand-Schuller-Christian Disease (HSCD) and eosinophilic granuloma (EG)-all of which have systemic involvement (although EG does not usually demonstrate any skin findings). In contrast, CSHH typically only involves the skin. The classic triad of symptoms associated with HSCD is diabetes insipidus, bone lesions, and exopthalmos. Eosinophilic granuloma is a localized histiocytic infiltrate in the bone. Like CSHH, LSD also occurs in babies, usually under the age of 1 year. The lesions are generally more pink-skin colored and occur in the flexural and seborrheic areas, unlike those of CSHH, which can occur anywhere on the body. Systemic involvement in LSD is variable, but commonly affects the lung, liver, bone and lymph nodes. There is considerable overlap in the skin lesions of CSHH and LSD, and as noted above, the histologic appearances of CSHH and LSD can be indistinguishable. Consequently, patients with a clinical presentation consistent with CSHH must be followed at least until the age of 3 months to be certain that the skin lesions resolve completely and do not recur. The patient should also be examined to rule out the development of systemic disease. It is now commonly thought that the different forms of LCH represent different ends of the spectrum of the same disease process. In this context, there will be many overlap cases and patients should be evaluated and followed closely.

Our patient was discharged to home after treatment of her bacteremia. Her skin lesions were rapidly resolving in the first week of life. She will follow up as an outpatient in clinic.

Presented by Drs. Chynna Steele and Susan Bayliss.
Thanks to Drs. Nathan Walk amd Anne Lind for the histopathology.

REFERENCES
1. Kapur P, Erickson C, Rakheja D, Carder KR, Hoang MP. Congenital self-healing reticulohistiocytosis (Hashimoto-Pritzker disease): Ten year experience at Dallas Children's Medical Center. JAAD. 2007:56:280-294.

2. Morgan KW, Callen JP. Self-healing congenital Langerhans cell histiocytosis presenting as neonatal papulovesicular eruption. J Cut Med Surg. 2001:5:486-489.

3. Ricart J, Jimenez A, Marquina A, Villanueva A. Congenital self-healing reticulohistiocytosis: report of a case and review of the literature. Acta Paediatr. 2004:92:426-429.

4. Savasan, S. An enigmatic disease: childhood Langerhans cell histiocytosis in 2005. Int J Dermatol. 2006:45:182-188.