|Year : 2021 | Volume
| Issue : 2 | Page : 97-98
Diverse and rare clinical manifestations of Langerhans cell histiocytosis
Pin-Hsuan Chiang1, Chi-Feng Yen1, I-Hsin Shih1, Guan-Hua Chen2, Chin-Yi Yang3
1 Department of Dermatology, Chang Gung Memorial Hospital; School of Medicine, College of Medicine, Chang Gung University, Taoyuan City, Taiwan
2 Department of Pathology, Chang Gung Memorial Hospital, Taoyuan City, Taiwan
3 Department of Dermatology, Chang Gung Memorial Hospital; School of Medicine, College of Medicine, Chang Gung University, Taoyuan City; Department of Dermatology, New Taipei Municipal TuCheng Hospital, New Taipei City, Taiwan
|Date of Submission||11-Sep-2020|
|Date of Decision||14-Jan-2021|
|Date of Acceptance||02-Mar-2021|
|Date of Web Publication||23-Jun-2021|
Dr. Chin-Yi Yang
Department of Dermatology, New Taipei Municipal Tucheng Hospital, No. 6, Section 2, Jincheng Road, Tucheng District, New Taipei City 236
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Chiang PH, Yen CF, Shih IH, Chen GH, Yang CY. Diverse and rare clinical manifestations of Langerhans cell histiocytosis. Dermatol Sin 2021;39:97-8
|How to cite this URL:|
Chiang PH, Yen CF, Shih IH, Chen GH, Yang CY. Diverse and rare clinical manifestations of Langerhans cell histiocytosis. Dermatol Sin [serial online] 2021 [cited 2022 Dec 3];39:97-8. Available from: https://www.dermsinica.org/text.asp?2021/39/2/97/319145
Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder that may involve bone, skin, pituitary gland, liver, spleen, hematopoietic system, lung, and lymph nodes. Herein, we report a case of multisystem LCH presenting with unusual cutaneous features which led to delays in diagnosis.
A healthy 1.5-year-old girl initially presented with scattered itchy papules with central umbilication on the face. Molluscum contagiosum (MC) were diagnosed in several hospitals. She was referred to our hospital because of worsening condition under over 6-month treatment. Cutaneous examination demonstrated multiple skin-colored and erythematous papules, and vesicles on the face, trunk, and extremities [Figure 1]a and [Figure 1]b. Crusted and ulcerated papules with yellowish purulent discharge on the left eyelid [Figure 1]b; subungual pustules with crusting, hemorrhage, and partial nail shedding on multiple fingernails and toenails [Figure 1]c; macerated erythema of perineum [Figure 1]d; moreover, crusted ulceration at the injection site of the Bacillus Calmette–Guérin (BCG) vaccine [Figure 1]e. Concomitant bacterial, fungal, and viral infections were suspected. However, survey including immunoassays and vesicle culture for herpes virus, and fungus culture of involved nails disclosed no evidence of active infection.
|Figure 1: Clinical manifestations of the patient. (a) Skin-colored papules with central umbilication. (b) Crusted erythematous papules on the face and ulcerated papules with yellowish purulent discharge on the left eyelid. (c) Subungual pustules with crusting and partial nail shedding. (d) Erythematous macerations on the perineum. (e) Ulceration with crusting at the Bacillus Calmette–Guérin injection site.|
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Pathology of the right sole lesion revealed a nodular dermal infiltration of pale cells containing grooved nuclei without Henderson-Patterson bodies [Supplementary Figure 1]a. Immunohistochemical staining for S100 [Supplementary Figure 1]b, CD1a [Supplementary Figure 1]c, and Langerin [Supplementary Figure 1]d were positive, confirming the diagnosis of LCH. Bone radiography showed an osteolytic lesion on the left proximal ulna and the biopsy result of bony lesion was consistent with LCH. The other staging workups including complete blood cell count, blood biochemistry tests of the liver and renal function, urine analysis, and osmolality, Chest X-ray, abdominal sonography, and bone marrow aspiration examination were negative. As a result, the patient was diagnosed with multisystem LCH with low-risk organ involvement.
First-line initial induction chemotherapy treatment with oral prednisolone (40 mg/m2/day) and intravenous vincristine (1.5 mg/m2) weekly was initiated for multisystem LCH with low-risk organ involvement. Due to limited improvement, the treatment was shifted to second-line therapy by adding methotrexate and mercaptopurine. This patient underwent a total course of 12-month treatment with initial induction chemotherapy followed by continuation therapy. The lesions were resolved with depressed scars [Figure 2]a 6 months after initial induction chemotherapy. However, recurrent cutaneous lesions which still mimicked MC [Figure 2]b were noted at 5 months after the completion of 12-month therapy and the patient restarted chemotherapy again.
|Figure 2: Clinical manifestations of the cutaneous lesions at 5 months after completion of chemotherapy during the follow-up visit. (a) Resolution of previous cutaneous lesions with residual depressed scars was noted on the face. Few recurrent papules on central face were noted. (b) Recurrent cutaneous lesions on left arm mimicked Molluscum contagiosum.|
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LCH commonly affected the children before age three. Skin features typically resemble seborrheic dermatitis, diaper dermatitis or eczematous dermatitis with poor response to treatment but are variable causing a high rate of initial misdiagnosis (16%).,, Hypopigmented or hyperpigmented macules, poikilodermatous plaques, tumors, ulcers, hemorrhagic lesions, and oral mucosa involvement have been reported in addition to the typical cutaneous features. Some patients may also have systemic symptoms such as fever and fatigue. The definitive diagnosis of LCH depends on clinical manifestations, histologic examination, and immunohistochemistry studies. Cutaneous manifestations are important clues for the diagnosis of LCH. Up to 90% of patients with skin manifestations are finally diagnosed with multisystem disease who need the aggressive therapy.,
Our case's initial manifestation mimicked the feature of molluscum without evidence of MC infection noted on histopathologic report. A molluscum-like presentation or LCH combined with MC is extremely rare, with 9 reported cases.,,, Only two cases showed co-existence of LCH and MC infection with histologic confirmation.,, Hatter et al. detected Molluscum contagiosum virus DNA in an excised specimen of LCH, indicating that Langerhans cell hyperplasia may occur secondary to MC. Another hypothesis is that expanding histiocytes recruited regulatory T-cells which inhibited antiviral cytotoxic T-cells causing MC virus infection. Age at onset may be a clue for diagnosis. Generally, the average age of MC infection patients is often older (5–10 years) than those with LCH.
Furthermore, nail involvement was only described in few cases. Our case illustrated the wide range of nail features of LCH, including subungual pustules, hyperkeratosis, and onycholysis. It should be differentiated from eczema, psoriatic nails, herpetic whitlow, and bacterial or fungal infection. Mataix et al. reported over 90% of cases with nail changes classified as multisystem disease and assumed that nail involvement might be an unfavorable predictor. Our patient was finally diagnosed with multisystem LCH with limited response to first-line therapy may be consistent with this finding.
Persistent ulceration with crusting of the BCG injection site which was similar to bacterial or atypical infection was found in our patient. Only one study mentioned the cutaneous reaction after vaccination in LCH, and the patient presented with red-blue nodules on both buttocks after diphtheria, tetanus, and pertussis vaccination injections. Nevertheless, no case of skin change after BCG vaccination injection in LCH has been reported previously.
In conclusion, our case presented with diverse and rare clinical features mimicking cutaneous infections in patient with immunodeficiency and such case has not been reported before. LCH may be self-limiting or life-threatening, depending on the affected organs. Early recognition of the cutaneous presentations and appropriate treatment are important to improve prognosis. This unique case may assist in further understanding the rare cutaneous features.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient's mother have given her consent for images and other clinical information to be reported in the journal. The patient's mother understands that name and initials will not be published, and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
Dr. I-Hsin Shih, an editorial board member of Dermatologica Sinica, had no role in the peer review process of or decision to publish this article. The other authors declared that they have no conflicts of interest.
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[Figure 1], [Figure 2]