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Year : 2021  |  Volume : 22  |  Issue : 4  |  Page : 374-377

Response of papillon–Lefevre syndrome to acitretin

Department of Dermato-Venereo-Leprology, Government Medical College and Hospital, Nagpur, Maharashtra, India

Date of Submission27-Feb-2021
Date of Decision15-Apr-2021
Date of Acceptance02-Aug-2021
Date of Web Publication01-Oct-2021

Correspondence Address:
Vaishali H Wankhade
Department of Dermatology Venereology Leprology, Government Medical College and Hospital, Nagpur, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpd.ijpd_156_20

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Papillon–Lefevre (PLS) is a rare autosomal recessive disorder of keratinization characterized by symmetric, trans-gradient type palmoplantar keratoderma (PPK), rapidly progressive periodontopathy, and precocious loss of dentition. The management of this condition is difficult and needs a combined approach of both dermatologist and periodontologist. Different treatment options tried previously include keratolytic agents such as salicylic acid, urea, topical steroids in combination with keratolytic, propylene glycol, and systemic retinoids such as etretinate, isotretinoin, and acitretin. Both skin and dental manifestations show good therapeutic responses to systemic retinoids. Thereby, we report a case of PLS in a young female child who showed an excellent response to oral acitretin therapy.

Keywords: Acitretin, palmoplantar keratoderma, trans-gradiens

How to cite this article:
Kowe PA, Lavanya P, Wankhade VH, Singh RP. Response of papillon–Lefevre syndrome to acitretin. Indian J Paediatr Dermatol 2021;22:374-7

How to cite this URL:
Kowe PA, Lavanya P, Wankhade VH, Singh RP. Response of papillon–Lefevre syndrome to acitretin. Indian J Paediatr Dermatol [serial online] 2021 [cited 2022 Jan 20];22:374-7. Available from: https://www.ijpd.in/text.asp?2021/22/4/374/327446

  Introduction Top

Inherited palmoplantar keratodermas (PPKs) are a heterogeneous group of disorders characterized by hyperkeratosis of the palms and soles and categorized into different syndromes based on associated clinical findings.[1] The Papillon–Lefèvre syndrome (PLS) was first described by French physicians Papillon and Lefevre in 1924 with the incidence of one to four cases per million population having onset between the ages of 1 and 4 years with no racial or sexual predilection.[2] It is characterized by diffuse PPK, premature loss of deciduous and permanent teeth, and a tendency to recurrent pyogenic infections of the skin and internal organs.[2] We report a case of PLS in an 8-year-old girl who had an excellent response to oral acitretin therapy.

  Case Report Top

An eight-year-old female child born of first-degree consanguineous marriage presented with thickening and scaling of the skin over palms, soles, knees, and elbows associated with premature loss of teeth since the age of 6 months. It started as small thick scaly lesion over palmar aspect of fingers and plantar surface of toes which gradually progressed into diffuse thickening of the palms and soles and extending over the dorsum of hands and feet with the involvement of wrist, ankle, knee, and elbow joints over the period of 5 years. There was a history of recurrent dental infection with premature loss of teeth since childhood. None of her family members had a similar complaint and there was no history of excessive sweating. Cutaneous examination revealed bilaterally symmetrical diffuse keratoderma of the palms and soles without surrounding erythema associated with scaling and fissuring extending over the dorsum of hands and feet with the involvement of wrist and ankle joints (transgradiens) [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d. Similar hyperkeratotic well-demarcated scaly plaques were seen over the bilateral elbow and knee joints [Figure 2]a and [Figure 2]b. Oral cavity examination showed wide spacing of teeth with absent upper lateral incisor teeth and high arched palate [Figure 3]a and [Figure 3]b. Hair and nail examination showed no abnormality. Based on history and clinical findings, we kept the differential diagnosis of PLS, Greither's disease (GD), and Haim–Munk syndrome (HMS). All routine blood investigations including serum lipid profile were within a normal range. Skin biopsy from sole revealed hyperkeratosis, parakeratosis, hypergranulosis with acanthosis consistent with the diagnosis of PPK [Figure 4]a and [Figure 4]b. Thus based on clinical presentation and histopathology a final diagnosis of PLS was made. The patient was started on capsule Acitretin 10 mg daily at night along with 10% urea and ammonium lactate lotion for local application. There was 50% improvement in transgradient PPK at 6 weeks [Figure 5]a, [Figure 5]b, [Figure 5]c, [Figure 5]d and 70%–80% improvement [Figure 6]a, [Figure 6]b, [Figure 6]c, [Figure 6]d at 12 weeks of acitretin therapy. There was a marked reduction of hyperkeratotic plaques over elbows and knee joints after 12 weeks of acitretin [Figure 7]a and [Figure 7]b. She has advised treatment of caries teeth and use of an extra soft brush for regular cleaning from the dental side. Monthly monitoring of her hematological parameters was within normal limits. After 3 months of treatment, the patient was shifted to a maintenance dose of 10 mg acitretin thrice a week for the next 3 months with no relapse of symptoms. Thereafter, the patient was reassured and counseled for regular use of emollients especially during the winter season, and proper dental care as advised by the periodontologist.
Figure 1: Keratoderma with scaly plaques and fissures over (a) palms (b) soles (c) dorsum of hands (d) dorsum of feet with transgradiens

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Figure 2: Well-demarcated hyperkeratotic plaques over (a) bilateral elbow and (b) knee joint

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Figure 3: Oral cavity showing (a) widely spaced teeth with lost upper lateral incisor (b) high arched palate

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Figure 4: (a) Scanner view of skin biopsy from plaque over sole revealed epidermis and dermis (H and E × 10) (b) hyperkeratotic epidermis and parakeratosis (blue arrow), hypergranulosis (red arrow) and acanthosis (green arrow) suggestive of palmoplantar keratoderma (H and E × 40)

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Figure 5: (a-d) 50% improvement with a reduction in scaling and thickening of plaques over hands and feet

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Figure 6: (a-d) 70%–80% improvement with flattening and reduced scaling of plaques over palms, soles, dorsum of hands and feet at 12 weeks

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Figure 7: (a and b) Flattening of keratoderma over elbows and knees at 12 weeks

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  Discussion Top

PLS come under the category of diffuse PPK involving two major components such as dermatological and periodontal changes. It is caused by homozygous mutation in CTSC gene on 11q 14 which encodes the lysosomal protease cathepsin C expressed in cells of the immune system such as nuclear leukocyte, in the lung, kidney, and other epithelial tissues. Its major functions are protein degradation and proenzyme activation which is impaired in PLS. In addition, neutrophil phagocytosis, natural killer cell cytotoxicity, and reactivity to T and B cell mitogens are decreased leading to a predisposition to pyogenic infections of the skin and internal organs.[3] Other features of PLS include pseudo-ainhum, calcification of dura, falx cerebri, tentorium cerebelli, choroid plexus, and intraabdominal abscess.[3] The differential diagnosis of PLS includes GD and HMS. GD manifests as diffuse transgradiens PPK with surrounding erythema, palmoplantar hyperhidrosis, nail changes, amputation of digits, and blistering.[4] HMS is characterized by arachnodactyly, onychogryphosis and acro-osteolysis in addition to the feature of PLS.[5] As PLS is a multifactorial entity a multidisciplinary approach of the dermatologist, pediatrician, and dentist are necessary for the therapeutic management and better outcome. Different treatment options that have been tried for PLS-associated PPK are topical keratolytic such as salicylic acid, urea, and propylene glycol along with emollients. For periodontitis maintaining good oral hygiene care, intermittent antibiotics for infections, and extraction of movable teeth are needed.[6] Systemic retinoids including acitretin, etretinate, and isotretinoin have been found to be effective for keratoderma observed in PLS especially in winter when PPK can worsen with painful fissures limiting daily activities.[7],[12] Among these, acitretin is found to be the most widely and safely used drug. It targets cytosolic proteins and intranuclear receptors where its metabolites bind to retinoic acid receptors leading to alteration of gene transcription which is responsible for its antiproliferative and anti-inflammatory effects. Thus, it normalizes epidermal cell proliferation, differentiation, and cornification in psoriasis and other disorders of cornification.[11] It is found to be effective in the dose of 0.4–1 mg/kg/day.[12],[13] Nazzaro et al. and Lee et al. reported that acitretin works effectively for both PPK and periodontal disease of which PPK responds and improves faster than periodontitis.[9],[13] There are few case reports of oral acitretin for PLS all of which show good results [Table 1]. However, relapse of PPK is observed as soon as acitretin is stopped, and hence, prolonged treatment is needed for maintaining remission and also for dental complaints it is to be continued till eruption of permanent teeth. Lacour et al. reviewed the data of 46 children with acitretin (0.4 mg/kg//) for 472 months and found that it is a safe and effective treatment in children with disorders of cornification.[14] Still one should be vigilant with regards to liver functions, hyperlipidemia, bone abnormality, and teratogenicity by appropriate monitoring while on long-term acitretin.
Table 1. Previous studies of Acitretin in PLS

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  Conclusion Top

Low-dose acitretin is a good therapeutic molecule for all symptoms of PLS and hence should be used judiciously with precautions and constant monitoring.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.


We would like to thank Dr Dharitri Bhat (Associate professor, Dept of pathology, Government medical college and hospital Nagpur) for helping us with histopathology reporting.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Oji V, Metze D, Traupe H. Inherited disorders of cornification. In: Griffiths C, Barker J, Bleiker T, editors. Rook's Textbook of Dermatology. 9th ed., Vol 65. Oxford: Wiley Blackwell; 2016. p. 46-7.  Back to cited text no. 1
Sarma N, Ghosh C, Kar S, Bazmi BA. Low-dose acitretin in Papillon-Lefèvre syndrome: treatment and 1-year follow-up. Dermatol Ther 2015;28:28-31.  Back to cited text no. 2
Oji V, Metze D, Traupe H. Inherited disorders of cornification. In: Griffiths C, Barker J, Bleiker T, editors. Rook's Textbook of Dermatology. 9th ed. Oxford: Wiley Blackwell; 2016. p. 65-61.  Back to cited text no. 3
Athanikar SB, Inamadar AC, Palit A, Sampagavi VV, Deshmukh NS. Greither's disease. Indian J Dermatol Venereol Leprol 2003;69:292-3.  Back to cited text no. 4
[PUBMED]  [Full text]  
Mohan RS, Verma S. Haim Munk syndrome: report of two siblings of northern India treated with acitretin. Indian J Dermatol Venereol Leprol 2011;77:252.  Back to cited text no. 5
[PUBMED]  [Full text]  
Ullbro C, Crossner CG, Nederfors T, Alfadley A, Thestrup-Pedersen K. Dermatologic, and oral findings in a cohort of 47 patients with Papillon-Lefevre syndrome. J Am Acad Dermatol 2003;48:345-51.  Back to cited text no. 6
Bergman R, Friedman-Birnbaum R. Papillon-Lefèvre syndrome: A study of the long-term clinical course of recurrent pyogenic infections and the effects of etretinate treatment. Br J Dermatol 1988;119:731-6.  Back to cited text no. 7
Sethuraman G, Malhotra AK, Khaitan BK, Sharma VK. Effectiveness of isotretinoin in Papillon–Lefèvre syndrome. Pediatr Dermatol 2005;22:378-9.  Back to cited text no. 8
Nazzaro V, Blanchet-Bardon C, Mimoz C, Revuz J, Puissant A. Papillon-Lefèvre syndrome. Ultrastructural study and successful treatment with acitretin. Arch Dermatol 1988;124:533-9.  Back to cited text no. 9
Balci DD, Serarslan G, Sangun O, Homan S. Acitretin for Papillon-Lefevre syndrome in a five-year-old girl. Indian J Dermatol Venereol Leprol 2008;74:71-3.  Back to cited text no. 10
[PUBMED]  [Full text]  
Pilkington T, Brogden RN. Acitretin: A review of its pharmacology and therapeutic use. Drugs 1992;43:597-627.  Back to cited text no. 11
Al-Khenaizan S. Papillon-Lefévre syndrome: The response to acitretin. Int J Dermatol 2002;41:938-41.  Back to cited text no. 12
Lee MR, Wong LC, Fischer GO. Papillon-Lefèvre syndrome treated with acitretin. Australas J Dermatol 2005;46:199-201.  Back to cited text no. 13
Lacour M, Mehta-Nikhar B, Atherton DJ, Harper JI. An appraisal of acitretin therapy in children with inherited disorders of keratinization. Br J Dermatol 1996;134:1023-9.  Back to cited text no. 14


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]

  [Table 1]


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