80

Congenital Self-Healing Reticulohistiocytosis Presenting as Hypopigmented Macules and Papules in a Neonate

Shyue-Luen Chang1 I-Hsin Shih1 Tseng-Tong Kuo2 I-Chieh Lai3 Ching-Chi Chi3 Chih-Hsun Yang1

Congenital self-healing reticulohistiocytosis, also known as Hashimoto-Pritzker disease) is a rare variant of Langerhans cell histiocytosis. It is characterized by developing multiple or sin-gle red-brown papules, nodules or vesicles at birth or first few weeks of life and involutes spon-taneously without systemic involvement of other organs. We report a rare case of female neonate presented with multiple white macules and papules on trunk. Langerhans cell histiocytosis is di-agnosed by histological examination and immunohistochemical study. We remind dermatologists to be aware of this rare presentation and should put it into differential diagnosis lists when facing hypopigmented lesions in a neonate. (Dermatol Sinica 26: 80-84, 2008)

Key words: Langerhans cell histiocytosis, Congenital self-healing reticulohistiocytosis, Hashimoto-Pritzker disease, Hypopigmentation

From the Department of Dermatology1 and Pathology2, Chang-Gung Memorial Hospital and Chang-Gung University College of Medicine, Taipei, Taiwan, and the Department of Dermatology, Chang-Gung Memorial Hospital, Chiayi , Taiwan3

Accepted for publication: January 7, 2008Reprint requests: I-Hsin Shih, MD, Department of Dermatology, Chang-Gung Memorial Hospital, No. 199, Tunghwa N. Rd., Tai-pei, Taiwan.TEL: 886-2-27135211 ext. 3399 FAX: 886-2-27191623 E-mail: ellis@adm.cgmh.org.tw

Case Report

INTRODUCTIONCongenital self-healing reticulohistio-

cytosis (CSHRH), a rare form of Langerhans cell histiocytosis, is typically presented at birth or in the newborn period with spontaneous regression. It is usually characterized by the eruption of multiple, disseminated, red-brown papules and nodules which may increase in size and number during the first few weeks of life without systemic signs.1 Skin lesions initially manifested by depigmented or hypop-igmented macules and papule had never been described before. We present a case of female neonate presented with multiple white macules and papules on trunk, which may mimic other hypopigmented diseases clinically.

CASE REPORTA 7-month-old girl in our clinic was

noted to have progressive white cutaneous eruption on her back, abdomen and chest. The patient’s mother said the eruption had been present one month after birth and was asymp-tomatic. There were no preceding papules or vesicles before the eruption. The patient had an unremarkable past medical history and no family history of similar lesions. The baby was otherwise healthy without fever, weight loss, dyspnea, mucosal involvement, hepatosple-nomegaly and lymphadenopathy. On physical examination, multiple small round scaleless white macules and papules were distributed on

81Dermatol Sinica, Jun 2008

Congenital Self-Healing Reticulohistiocytosis

her back, abdomen and chest. (Fig. 1) There is no lesion on the extremities and head. The margins of the lesion is irregular. (Fig. 2)

A skin biopsy from the papule revealed hyperkeratosis, focal parakeratosis, mild acan-thosis, and histiocytes in papillary dermis and in epidermis. Occasional eosinophils are also seen. (Fig. 3) Immunohistochemical stains showed that the histiocytes were positive for S-100 and CD1a (Fig. 4) and confirm the diag-nosis of Langerhans cells histiocytosis.

The patient was referred to pediatric he-matologist for further survey and revealed only cutaneous involvement. The skin lesions com-pletely regressed spontaneously 3 months later and did not recur in one and half year follow-up.

DISCUSSIONLangerhans cell histiocytosis is a dis-

ease of unknown cause characterized by a clonal proliferation of S-100 and CD1a posi-tive activated Langerhans cells.2-3 Four main forms were included: Letterer-Siwe disease, Hand-Schüller-Christian disease, eosinophilic granuloma, and Hashimoto-Pritzker disease (congenital self-healing reticulohistiocytosis).4-5

In neonates, cutaneous changes were the most common initial manifestation in Langerhans cell histiocytosis.6

CSHRH is a rare variant of Langerhans cell histiocytosis, typically presents at birth or first few weeks of life and involutes spon-taneously with no systemic involvement. It is characterized by multiple red, violaceous, or brownish, firm, painless papules and crusts scattered all over the face, scalp, trunk, limbs, palms and soles of the feet, and some patients may have a vesicular eruption, or sparse nod-ules.7

Our patient presented skin eruptions with-out lesions of the mucous membrane and no systemic symptoms. Histopathologically, infil-trations of Langerhans cells in papillary dermis and in epidermis with occasional eosinophils

were seen. The skin lesions disappeared spon-taneously after 8 months and did not reappear during one and half year’s follow-up. In view of the histology, dermatological lesions and evolution, the diagnosis of CSHRH should be considered.

Noteworthily, our patient initially mani-fested with multiple small round white macules and papules on her back, abdomen and chest, which have never been reported before. Al-though firm, red-brown, painless, papulonod-ules or vesicles and crusts followed by residual hypopigmented or hyperpigmented scar had been mentioned in previous article,1 in our pa-tient, according to her mother’s description, no such previous episode was noted. Besides, skin biopsy of the hypopigmented papule revealed active disease activity, instead of residual scar or only pigment changes. However, the pos-sibility of unawareness of previous skin lesions by her families could not be totally excluded.

There are several differential diagnoses for multiple hypopigmented macules and pap-ules in a neonate, such as clear cell papulosis, pityriasis versicolor, nevus depigmentosus, vitiligo, pityriasis alba, post inflammatory hypopigmentation, hypomelanosis of Ito, and incontinentia pigmenti.

Clear cell papulosis are hypopigmented macules or barely palpable papules follow-ing the milk line on anterior trunk.8 They only rarely developed on back.9 Pityriasis versicolor can be excluded by potassium hydroxide ex-amination. Nevus depigmentosus is generally known to be a congenital, nonfamilial disorder characterized by hypopigmented lesion that re-mains stable in size and distribution throughout life. Most patients with nevus depigmentosus had one lesion or at least less than 10 lesions.10

Vitiligo is an acquired disorder with uniformly milk- or chalk-white color with discrete mar-gin. The natural course of vitiligo is unpredict-able, but often shows abrupt onset, followed by progression for a time, and then a period of stability.10 Pityriasis alba is characterized by

82 Dermatol Sinica, Jun 2008

Shyue-Luen Chang, et al

the presence of ill-defined, hypopigmented, round-to-oval, scaling patches on the face, upper arms, neck, or shoulders. The legs and trunk are less commonly involved.11 Post in-flammatory hypopigmentation can be excluded by previous history of previous inflammatory conditions or medication. Hypomelanosis of Ito shows a familial tendency and is usually associated with systemic abnormalities. It is characterized by hypopigmented patches in streaks and whorls.12 Incontinentia pigmenti is an X-linked dominant neurocutaneous syn-

drome with frequent systemic involvement. Typically, the cutaneous findings generally progress through 4 distinct characteristic stag-es.13 By histopathological examinations, diag-nosis of Langerhans cell histiocytosis could be easily made.

In conclusion, due to the diversity of the clinical manifestation and the morphological similarity to other entities, cutaneous Langer-hans cell histiocytosis could be a diagnostic challenge.14 We report a rare case of congenital self-healing reticulohistiocytosis manifested

Fig. 1Progressive white cutaneous lesions were noted on back, ab-domen and chest.There was no lesion on extremities and head.

Fig. 2Close-up view revealed multiple small round scaleless white macules and papules with irregular margin.

Fig. 3Skin biopsy showed hyperkeratosis, focal parakeratosis, mild acanthosis, and histiocytes in papillary dermis and in epi-dermis. Occasional eosinophils were also seen in other area. (H&E, original magnification x400)

Fig. 4 Immunohistochemical stains showed that the histiocytes were positive for CD1a (left) and S-100 (right). (Original magnification x200)

83Dermatol Sinica, Jun 2008

Congenital Self-Healing Reticulohistiocytosis

by multiple small round white macules and papules on trunk in a neonate. We remind dermatologists to be aware of this rare presen-tation and when multiple hypopigmented or depigmented macules or papules were noted in a neonate. Langerhans cell histiocytosis should be put into differential diagnosis lists with systemic survey and long-term follow up if pa-thology confirms the diagnosis.

REFERENCES1. Walia M, Paul P, Mishra S, et al.: Congenital

Langerhans cell histiocytosis: the self-healing vari-ety. J Pediatr Hematol Oncol 26: 398-402, 2004.

2. Willman CL, Busque L, Griffith BB, et al.: Langer-hans’-cell histiocytosis (histiocytosis X)--a clonal proliferative disease. N Engl J Med 331: 154-160, 1994.

3. Kapur P, Erickson C, Rakheja D, et al.: Congeni-tal self-healing reticulohistiocytosis (Hashimoto-Pritzker disease): ten-year experience at Dallas Children’s Medical Center. J Am Acad Dermatol 56: 290-294, 2007.

4. Lichtenstein L: Histiocytosis X; integration of eosinophilic granuloma of bone, Letterer-Siwe disease, and Schuller-Christian disease as related manifestations of a single nosologic entity. AMA Arch Pathol 56: 84-102, 1953.

5. Hashimoto K, Pritzker MS: Electron microscopic study of reticulohistiocytoma. An unusual case of

congenital, self-healing reticulohistiocytosis. Arch Dermatol 107: 263-270, 1973.

6. Minkov M, Prosch H, Steiner M, et al.: Langerhans cell histiocytosis in neonates. Pediatr Blood Cancer 45: 802-807, 2005.

7. Ricart J, Jimenez A, Marquina A, et al.: Congenital self-healing reticulohistiocytosis: report of a case and review of the literature. Acta Paediatr 93: 426-429, 2004.

8. Kuo TT, Huang CL, Chan HL, et al.: Clear cell papulosis: report of three cases of a newly recog-nized disease. J Am Acad Dermatol 33: 230-233, 1995.

9. Benouni S, Kos L, Ruggeri SY, et al.: Clear cell papulosis in Hispanic siblings. Arch Dermatol 143: 358-360, 2007.

10. Kim SK, Kang HY, Lee ES, et al.: Clinical and histopathologic characteristics of nevus depigmen-tosus. J Am Acad Dermatol 55: 423-428, 2006.

11. Lin RL, Janniger CK: Pityriasis alba. Cutis 76: 21-24, 2005.

12. Rubin MB: Incontinentia pigmenti achromians. Multiple cases within a family. Arch Dermatol 105: 424-425, 1972.

13. Berlin AL, Paller AS, Chan LS: Incontinentia pig-menti: a review and update on the molecular basis of pathophysiology. J Am Acad Dermatol 47: 169-187; quiz 88-90, 2002.

14. Querings K, Starz H, Balda BR: Clinical spectrum of cutaneous Langerhans’cell histiocytosis mimick-ing various diseases. Acta Derm Venereol 86: 39-43, 2006.

84 Dermatol Sinica, Jun 2008

Shyue-Luen Chang, et al

以白色斑疹及丘疹為表現的先天性自癒性網狀組織

細胞增生症

張學倫1　施一新

1　郭承統

2　賴義傑

3　紀景琪

3　楊志勛

1

先天性自癒性網狀組織細胞增生症是蘭格罕氏組織細胞增生症中罕見的一種型態。其特

徵是在剛出生或出生數週內在皮膚產生多個或單一紅棕色丘疹、腫塊或水疱而不侵犯其他器

官或系統，且會自行痊癒。我們報告一位女嬰以白色斑疹及丘疹呈現於軀幹為表徵。藉由病

理檢查及免疫組織學檢查證實為蘭格罕氏組織細胞增生症。我們提醒皮膚科醫師注意先天性

自癒性網狀組織細胞增生症之罕見表現方式；當嬰兒身上呈現白色病灶時，應將本病列入鑑

別診斷。（中華皮誌：26: 80-84, 2008）