International Journal of Current Research and Review
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IJCRR - 9(21), November, 2017

Pages: 54-57

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A Study of Adult Onset Generalized Eruptive Langerhans Cell Histiocytosis with Rare Association of Nail Pterygium

Author: Sunanda Mahajan, Vikram Lahoria, Vidya Kharkar, Uday Khopkar

Category: Healthcare

Abstract:Background: Langerhans cell histiocytosis(LCH) is a rare proliferative disease which generally affects children and rarely, adults. LCH in adults first presenting in the skin is very rare and often it is misdiagnosed as it mimics number of common skin conditions. Nail changes are another cutaneous feature which is not frequently described in adults.
Objectives and Methods: To present two new cases of adult LCH and a review of the literature of generalized cutaneous LCH in adults.
Results: Two adults with widespread papulo-nodular cutaneous eruptions in seborrheic distribution. Both the cases had palmoplantar purpuric papules and involvement of nails with pterygium formation, which is a rare finding not frequently reported in LCH. There was pituitary involvement in the form of diabetes insipidus in both the cases though it was clinically symptomatic in only first case. Diagnosis of both the patients was established on the basis of histopathology and immunohistochemistry.
Conclusions: Extensive cutaneous and nail involvement (nail dystrophy and pterygium) is possible in adult onset LCH. Thus, high index of suspicion is necessary to make the diagnosis.

Keywords: Adult onset, Generalised, Pterygium, Langerhan cell histiocytosis

Full Text:

Introduction

Langerhans cell histiocytosis (LCH) is a rare disorder which is characterized by clonal proliferation of dendritic cells and mainly affects children under 10 years of age, although it can occur at any age, it is rarely reported in adults (1). It comprises a wide range of clinical presentations depending upon the organs it affects. The clinical course and prognosis of LCH is diverse which ranges from a spontaneously regressing single lesion to a life-threatening multisystem disease with rapid progression and sometimes even death. In adults, lungs are the most commonly involved system followed by bones and skin (2,3). Cutaneous lesions in LCH can be the great pretender and mimics number of common dermatoses(4) it creates more confusion when it is the presenting feature , which is rarely seen in adults. Nail changes are another cutaneous feature which is not frequently described in adults(9).

Objectives and Methods: Two new cases of adult LCH were studied with their complete workup and a review of the literature of generalized cutaneous LCH in adults.

Results: Two adults presented with widespread papulo-nodular cutaneous eruptions in seborrheic distribution of 2 years and 5 years duration respectively. Both the cases had palmoplantar purpuric papules and involvement of nails with pterygium formation, which is a rare finding not frequently reported in LCH. There was pituitary involvement in the form of diabetes insipidus in both the cases though it was clinically symptomatic in only first case. Diagnosis of both the patients was established on the basis of histopathology and immunohistochemistry.

Case 1

A 22 year old unmarried male presented with sudden onset of skin coloured to red raised itchy lesions over face which progressed gradually to become generalized over the next 2 years which showed ulcerations over the flexures since last 6-8 months. The patient had loss of appetite with recent weight loss (5 kgs in last 6 months) and increase in thirst and frequency of micturition.

Examination revealed multiple erythematous and translucent umbilicated papules coalescing to form plaques intermixed with hemorrhagic papules, crusts and pustules distributed in seborrheic pattern. Dirty greasy scales matted with purulent discharge were seen over the scalp. Both palms and soles showed punctate purpuric micropapules. All twenty nails were dystrophic with erythematous papules and pustules periungually. Two finger nails of left hand showed pterygium (figure 1a and 1b). Papular lesions were seen over the lips and hard palate. Systemic examination was uneventful.

Complete blood counts with biochemical tests were within normal limits. Urine osmolality was low 195 mosm/kg while serum osmolality was slightly high, 303mosm/kg. Water deprivation test was positive indicating central diabetes insipidus. Serum FSH, LH and serum testosterone levels were lower than normal limits.

Biopsy done from one of the papules showed lichenoid infiltrate in upper dermis and infiltrate consisting predominantly of large histiocytes with kidney shaped nucleus with few lymphocytes. The cells stained positively with CD1a and S100 (figure 1c and 1d).

X-ray skull showed enlarged sella turcica which was supported by MRI and CT (plain) scan brain, suggestive of hypophysitis. Bone scan showed no evidence of skeletal involvement.PET scan showed hyper metabolism in the axilla, groin and perianal region with focal hyper metabolism in the spleen.

A final diagnosis of adult onset langerhans cell histiocytosis with pituitary and spleen involvement (multisystem disease with high risk group) was made.

The patient was started on Cytarabine, but showed no improvement after 4 cycles. Hence was switched to Cladiribine chemotherapy, following which significant improvement was seen after 6 cycles. Maintenance therapy was given in the form of 6-mercapto-purine(50mg) daily with methotrexate (25mg) once weekly for 1 month. PET-CT scan done after 11 months of chemotherapy showed no evidence of any metabolically active lesion (figure 1e).

For central diabetes insipidus patient was started with intranasal desmopressin daily at night which has to be maintained lifelong.

Case 2

A 48 year old male patient presented with minimally itchy multiple red raised lesions over legs since 5 years which gradually spread to become generalised over the next 3 years. Examination revealed multiple erythematous papules, pustules and nodules intermixed with umbilicated translucent papules over seborrheic distribution with few of them showing haemorrhagic crusts. Periungual region showed pustules and haemorrhagic crusts with dystrophic nails and toe nails showing pterygium formation. Multiple punctate purpuric papules with pustules and few keratotic papules were seen over soles (figure 2a and 2b). An erosive plaque with a few papules was present over the hard palate. Systemic examination was normal.

Complete blood counts and biochemical tests were within normal limits. Urine osmolality was low, 221mosm/kg while serum osmolality was normal, 289mosm/kg. Water deprivation test was positive indicating central diabetes insipidus, although the patient was asymptomatic. Serum FSH, LH and serum testosterone levels were lower than normal limits.

Biopsy from the papular lesion showed dense and diffuse nodular infiltrate in the dermis consisting of histiocytes having reniform nuclei and abundant cytoplasm with lymphocytes and a few eosinophils. On immunohistochemistry CD 1a and S100 were positive (figure 2c and 2d).

X-ray Skull, X-rays long bones, MRI (Brain), bone scan and PET-CT scan were normal.

The diagnosis of adult onset Langerhans cell histiocytosis with pituitary involvement (multisystem disease low risk group) was established. The patient was started on oral Thalidomide(150mg) per day

Discussion

Langerhans cell histiocytosis (LCH) is characterized by proliferation and infiltration of organs by pathological Langerhans cells. The aetiology and pathogenesis of LCH still remains largely undefined. The clinical manifestations of the disease are largely related to the pattern of infiltration of the organs and organ systems involved which includes bone, skin, hypothalamus, liver, lung and lymph nodes(6). It generally affects children with peak incidence at the age of 1-3 years and annual incidence of 4-5 cases per million. However, adult onset LCH is rare with annual incidence rate of 1-2 cases per million (1).

Although the features of this disease are well described in children, they remain poorly defined in adults, due to the rarity of this condition in adults. Thus the optimal treatment is not yet established (3).

According to the report of the International Registry of the Histiocyte Society on adult LCH (IRHSA), which studied the clinical characteristics of 274 cases across 13 nations, single-system disease accounts for 31.39% while multisystem disease was seen in 68.61%. Most common presenting symptoms were local pain(34%), particularly due to bone involvement, weight loss (11%), and fever (10%). Lung was the most frequently involved organ system followed by bone and then the skin(3).

Langerhans cell histiocytosis (LCH) in adults first presenting in the skin is very rare(5), and often it is misdiagnosed as it mimics number of common skin conditions, as seen in both our patients. The development of systemic findings may occur months to years after the initial presentation of skin manifestations. Both the patients had long standing skin eruptions, 2 years in first case and 5 years in second case before presenting to us. Predominant sites of cutaneous involvement typically include the seborrheic pattern with translucent papules being the typical lesions. These lesions frequently show scaling or crusting (4). Generalised skin eruptions are commonly seen in childhood LCH, but it is rarely seen in adults. However both our patients had extensive skin eruption, which is not yet reported in India to best of our knowledge. Various nail changes are well reported in childhood LCH and are considered as bad prognostic factor (7).It includes paronychia, onycholysis, subungual hyperkeratosis and purpuric striae of the nail bed. However in adults it is rare to observe such nail changes, especially pterygium formation, which is seen in both of our patients. Only one case of adult onset lch with pterygium formation has been reported so far (8).

Originally classified into Hand-Schuller-Christian disease, Letterer-Siwe disease, and Eosinophilic Granuloma, is not used anymore. The current classification which is developed by the Histiocyte Society provides uniform criteria for the diagnosis and clinical evaluation of patients. According to the current classification it is divided into a single system LCH (SS-LCH), in which one of the organs is affected and multisystem LCH (MS-LCH) involving at least two organs. The MS-LCH is subdivided into 'low-risk' and 'high-risk' ones. Low-risk patients have no involvement of 'high-risk' organs (liver, lungs, spleen, hematopoietic cells) (10)

Diabetes insipidus (DI) is one of the most peculiar endocrine complications of LCH that can predate the diagnosis or develop anytime during the course of the disease and is found in up to 30% of patients. The risk of development of diabetes insipidus among adults with LCH is probably equal to or even greater than that of children with LCH. Anterior pituitary dysfunction (APD) is found in up to 20% of patients, almost always with DI (4).

Growth hormone deficiency (GHD) is the most frequent disease-related APD found in up to 50% of patients with DI. While gonadotropin deficiency is the second most common deficiency, presenting with menstrual disturbances in women and decreased libido in men (4).Both our cases had DI with APD, although there was no symptoms of DI in the second case.

Conclusion

These cases illustrate that extensive cutaneous and nail involvement (nail dystrophy and pterygium) is possible in adult onset LCH. Thus, high index of suspicion is necessary to make the diagnosis.

Even though asymptomatic, all patients should undergo a careful multidisciplinary evaluation and periodic follow-up to screen for possible asymptomatic localisation that could warrant prompt treatment and may prevent progression to systemic disease.

Such patients need to be treated at tertiary centre because the management is multidisciplinary which require care of oncologists, dermatologists and endocrinologists

Acknowledgement:

Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.

Source of Funding : none

Conflict of interest : none

References:

  1. Abla O, Egeler RM, Weitzman S. Langerhans cell histiocytosis: current concepts and treatments. Cancer Treat Rev 2010;36:354-9
  2. Götz G1, Fichter J. Langerhans'-cell histiocytosis in 58 adults. Eur J Med Res2004; 9(11):510-4.
  3. Aricò, M. et al. Langerhans cell histiocytosis in adultsReport from the International Registry of the Histiocyte Society. European Journal of Cancer 2003;Volume 39,Issue 16:2341 - 2348,.
  4. Girschikofsky M, Arico M, Castillo D. Management of adult patients with Langerhans cellhistiocytosis: recommendations from an expert panel on behalf of Euro-Histio-Net. Orphanet J Rare Dis 2013;8:72
  5. Edelbroek, J.R. et al. Langerhans cell histiocytosisfirst presenting in the skin in adults: frequent association with a second haematological malignancy. British Journal of Dermatology 2012;167:1287-1294
  6. Arico` M, Egeler RM. Clinical aspects of Langerhans cell histiocytosis. Hematol/OncolClin North Am 1998; 12:247-258.
  7. Penwadee Timpatanapong, Phongjan Hathirat, Parttraporn Isarangkura; Nail Involvement in Histiocytosis XA 12-Year Retrospective Study. ArchDermatol 1984;120(8):1052-1056.
  8. Moravvej, Hamideh,Yousefi, MaryamandBarikbin, Behrooz. An unusual case of adult disseminated cutaneous Langerhans cell histiocytosis. Dermatology Online Journal 2006; 12(6):13.
  9. Jain, S., Sehgal, V. N. and Bajaj, P. Nail changes in Langerhans cell histiocytosis. Journal of the European Academy of Dermatology and Venereology 2000; 14:212-215.
  10. Histiocyte Society 2009. Langerhans cell histiocytosis evaluation and treatment guidelines. Histocyte Society online. 2009. cited 2010-02.

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Awards, Research and Publication incentive Schemes by IJCRR

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One article from every issue is selected for the ‘Best Article Award’. Authors of selected ‘Best Article’ are rewarded with a certificate. IJCRR Editorial Board members select one ‘Best Article’ from the published issue based on originality, novelty, social usefulness of the work. The corresponding author of selected ‘Best Article Award’ is communicated and information of award is displayed on IJCRR’s website. Drop a mail to editor@ijcrr.com for more details.

Women Researcher Award:

This award is instituted to encourage women researchers to publish her work in IJCRR. Women researcher, who intends to publish her research work in IJCRR as the first author is eligible to apply for this award. Editorial Board members decide on the selection of women researchers based on the originality, novelty, and social contribution of the research work. The corresponding author of the selected manuscript is communicated and information is displayed on IJCRR’s website. Under this award selected women, the author is eligible for publication incentives. Drop a mail to editor@ijcrr.com for more details.

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‘Emerging Researcher Award’ is instituted to encourage student researchers to publish their work in IJCRR. Student researchers, who intend to publish their research or review work in IJCRR as the first author are eligible to apply for this award. Editorial Board members decide on the selection of student researchers for the said award based on originality, novelty, and social applicability of the research work. Under this award selected student researcher is eligible for publication incentives. Drop a mail to editor@ijcrr.com for more details.


Best Article Award

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A study by Muhas C. et al. entitled \"Study on Knowledge & Awareness About Pharmacovigilance Among Pharmacists in South India\" is awarded Best article for Vol 14 issue 22
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A study by Singh R. et al. entitled \"A Prospective Study to Find the Association of Astigmatism in Patients of Vernal Keratoconjunctivitis (VKC) in a Tertiary Health Care Centre in India (Vindhya Region MP)\" is awarded Best Article for Vol 14 issue 15
A Study by Humaira Tahir et al. entitled "Comparison of First Analgesic Demand after Major Surgeries of Obstetrics and Gynecology between Pre-Emptive Versus Intra-Operative Groups by Using Intravenous Paracetamol: A Cross-Sectional Study" is awarded Best Article for Vol 14 issue 14
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A Study by Manoj KP et al. entitled "A Randomized Comparative Clinical Trial to Know the Efficacy of Ultrasound-Guided Transversus Abdominis Plane Block Against Multimodal Analgesia for Postoperative Analgesia Following Caesarean Section" is awarded Best Article Award of Vol 13 issue 23
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A Study by Sindhu Priya E S et al. entitled "Neuroprotective activity of Pyrazolone Derivatives Against Paraquat-induced Oxidative Stress and Locomotor Impairment in Drosophila melanogaster" is awarded Best Article for Vol 12 issue 23
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A Study by Varsha M. Shindhe et al. entitled "A Study on Effect of Smokeless Tobacco on Pulmonary Function Tests in Class IV Workers of USM-KLE (Universiti Sains Malaysia-Karnataka Lingayat Education Society) International Medical Programme, Belagavi" is awarded Best article of Vol 12 issue 14, July 2020
A study by Amruta Choudhary et al. entitled "Family Planning Knowledge, Attitude and Practice Among Women of Reproductive Age from Rural Area of Central India" is awarded Best Article for special issue "Modern Therapeutics Applications"
A study by Raunak Das entitled "Study of Cardiovascular Dysfunctions in Interstitial Lung Diseas epatients by Correlating the Levels of Serum NT PRO BNP and Microalbuminuria (Biomarkers of Cardiovascular Dysfunction) with Echocardiographic, Bronchoscopic and HighResolution Computed Tomography Findings of These ILD Patients" is awarded Best Article of Vol 12 issue 13 
A Study by Kannamani Ramasamy et al. entitled "COVID-19 Situation at Chennai City – Forecasting for the Better Pandemic Management" is awarded best article for  Vol 12 issue 12
A Study by Muhammet Lutfi SELCUK and Fatma entitled "Distinction of Gray and White Matter for Some Histological Staining Methods in New Zealand Rabbit's Brain" is awarded best article for  Vol 12 issue 11
A Study by Anamul Haq et al. entitled "Etiology of Abnormal Uterine Bleeding in Adolescents – Emphasis Upon Polycystic Ovarian Syndrome" is awarded best article for  Vol 12 issue 10
A Study by entitled "Estimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata" is awarded best article for  Vol 12 issue 09
A Study by Ilona Gracie De Souza & Pavan Kumar G. entitled "Effect of Releasing Myofascial Chain in Patients with Patellofemoral Pain Syndrome - A Randomized Clinical Trial" is awarded best article for  Vol 12 issue 08
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A study by Karanpreet et al "Pregnancy Induced Hypertension: A Study on Its Multisystem Involvement" is given Best Paper Award for Vol 10 issue 09

List of Awardees

A Study by Ese Anibor et al. "Evaluation of Temporomandibular Joint Disorders Among Delta State University Students in Abraka, Nigeria" from Vol 13 issue 16 received Emerging Researcher Award


A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" from Vol 13 issue 06 received Emerging Researcher Award


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Disclaimer: International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal.



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International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal

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