Jadassohn Lewandowsky Syndrome: A Rare Entity

Transcription

15 March 2005
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601465/?rep...
Indian J Dermatol. 2015 Sep-Oct; 60(5): 524.
PMCID: PMC4601465
doi: 10.4103/0019-5154.159665
Anupama Manohar Prasad, Yugandar Inakanti, and Shiva Kumar
From the Department of DVL, P.E.S. Institute of Medical Sciences and Research, Kuppam, Andra Pradesh, India
Address for correspondence: Dr. Yugandar Inakanti, Department of DVL, P.E.S. Institute of Medical Sciences and Research, Kuppam - 517
425, Chittoor District, Andhra Pradesh, India. E-mail: [email protected]
Received 2014 Nov; Accepted 2015 Jan.
Copyright : © Indian Journal of Dermatology
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which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are
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Abstract
Pachyonychia congenita (PC) is a rare autosomal dominant genodermatosis characterized by hyperkeratosis
affecting the nails and palmoplantar areas, oral leucokeratosis, and cystic lesions. It is classically
subdivided into two major variants, PC-1 (Jadassohn–Lewandowski syndrome) and PC-2 (Jackson-Lawler
syndrome), according to the localization of the mutations in the KRT6A/KRT16 or KRT6B/KRT17 genes,
respectively. We report a 9-year-old male patient with a history of thickened, discolored nails, raised spiny
skin lesions all over the body since birth with focal plantar keratoderma and absence of natal teeth.
Keywords: Jadassohn–Lewandowski syndrome, keratins, nails, pachyonychia congenita, palmoplantar
keratoderma
What was known?
Jadassohn–Lewandowski syndrome is an autosomal dominant skin disorders characterized
predominantly by thickened nails, palmoplantar hyperkeratosis, keratosis pilaris, hyperkeratotic
follicular papules on the sites of friction, hair abnormalities and hyperhidrosis of the palms and soles.
These disorders have been suggested to be due to mutations in paired keratins.
Introduction
Pachyonychia congenita (PC) describes a group of rare autosomal dominant skin disorders characterized
predominantly by dystrophic, thickened nails and painful and highly debilitating palmoplantar
hyperkeratosis.[1,2]
Müller made one of the first documented observations of PC in 1904.[3] The next reports were published in
1905 by Wilson[4] and in 1906 by Jadassohn and Lewandowsky.[5] With a base on phenotypes, PC is
classified in four types: PC I to III and PC tarda.[6,7]
The objective of this case report is to describe the clinical features of PC-I. Although with inherent
limitations of a single case, this report may contribute to better understanding about this rare condition.
Case Report
A 9-year-old male born at term to non consanguineous parents was referred to our outpatient clinic for
evaluation of thickened nails starting at the age of 6 months.
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He presented with history of pinhead-sized yellowish spiny skin lesions all over body noted at birth that
had slowly grown during the first year of age and abnormalities nails. No history of natal or neonatal teeth
was there. The patient intelligence was normal. No similar complaints in family.
Physical examination showed:
Skin: Multiple follicular discrete papules present over the face, upper chest, buttock, elbow, knees
and flexures [Figures 1 and 2]
All 20 nails were thickened, yellowish discoloration with increased curvature and subungual
hyperkeratosis [Figures 3–5]
Focal plantar keratoderma [Figure 6]
Oral mucosa: Mucosal leucokeratosis [Figure 7]
There were no abnormalities in examination of palms, otolarynx and ophthalmology.
All laboratory investigations were within normal limits. KOH mounts of toe and finger nails were negative
for fungal elements. Histopathology examination of Follicular keratotic papule showed follicular plugging,
hyperkeratosis and acanthosis. A skin biopsy of sole showed marked hyperkeratosis, acanthosis, moderate
hypergranulosis and minimal dermal inflammatory infiltration. Based on characteristic clinical findings and
histopathology features, diagnosis of PC type 1 or Jadassohn–Lewandowski syndrome was confirmed.
Discussion
PC is a rare, autosomal dominant disorder characterized by triad of subungual hyperkeratosis with
accumulation of hard keratinous material beneath the distal portion of the nails, lifting the nails from the
nail bed, keratosis palmaris et plantaris with thick callosities, especially on the soles and thick white areas
on the oral mucosa.[8] Other associated features which may occur include keratosis pilaris, hyperkeratotic
follicular papules on the sites of friction, hair abnormalities and hyperhidrosis of the palms and soles. These
disorders have been suggested to be due to mutations in paired keratins, K6a/K16 (in PC1) and K6b/K17
(in PC2). According to these mutations, various clinical variants have been described:
PC-I or Jadassohn–Lewandowski syndrome (MIM #167200) is a common entity characterized by
onychogryposis on all the digits (100%), hyperkeratosis of the palmo plantar (50-90%) and of extensor
areas, follicular keratosis (37%), oral (50-75%) or laryngeal (6-15%) leukokeratosis, acral hyperhidrosis
(20-75%) and blisters (36%).[5,6,7,8,9,10,11,12]
In patients with PC-II or Jackson–Lawler syndrome (MIM #167210), main changes are natal or neonatal
teeth (15-50%), cutaneous cystic lesions (25%), disorders in scalp and eyebrow hairs (9-25%), in addition
to corneal dystrophy (8%); moreover, the nail hyperkeratosis is less accentuated in PC-II than in
PC-I.[6,9,10,11,12]
PC-III (Schafer-Brunauer syndrome) shows combined features of type 1 and 2 with angular cheilosis,
cataract and corneal dyskeratosis.[7] Despite recent advances in genetic analysis, misdiagnosis can occur
because same mutations may show diverse features.
A fourth variant, PC tarda, has also been described and is characterized by a later onset that ranges from
late childhood to middle ages. Other rare variants include PC with only nail involvement.
Pathogenesis Keratins
are structural proteins that promote the integrity of epithelial cells. As a result,
mutations in the genes encoding keratins lead to cell fragility.[1] The skin expresses the largest number of
keratin genes of any organ in body. PC is caused by mutations in five keratin genes KRT6a, KRT6b, KRT6c,
KRT16 and KRT17 which are expressed only in palmo plantar skin, the nail bed, pilosebaceous unit and
oral mucosa, leading to selective involvement of these sites in PC.[1]
PC is an autosomal dominant disorder. More than 45% of cases appear spontaneously
with no family history of PC. Given the overlapping clinical presentation with other genetic disorders, only
genetic testing can confirm the PC diagnosis.
Genetic Diagnosis
With nearly 100 distinct PC mutations now identified, correlating the signs of PC with specific mutations
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and genes has led to a new classification system of PC, now classified into five subgroups corresponding to
the underlying genetic defect: PC-K6a, PC-K6b, PC-K6c, PC-K16 and PC-K17.
Histological Findings Histological
examination of plantar hyperkeratosis plaques reveals an acanthotic
epidermis with parakeratosis and orthokeratosis compatible with rapid keratinocyte proliferation and
differentiation. Cytologic atypical is not seen.
Complications like respiratory distress due to laryngeal leucokeratosis and acroosteolysis, malignant
changes in palmoplantar lesions can occur in PC.
Treatment
Treatment options for PC fall into four broad categories:
Non-invasive (mechanical) e.g. abrasion with some hand tool
Invasive (surgical) e.g. electrofulgration, excision
Chemical methods using urea, propylene glycol, alpha hydroxy acid
Pharmacological (vitamin A, retinoid), all basically targeted at reducing the hyperkeratosis involving
different sites.
When the familial mutation is known, genetic counseling can be done and if required, prenatal diagnosis
can be done at early stage of pregnancy by chorionic villi biopsy. In our case, we advised keratolytics and
oral isotretinoin.
Conclusion
PC is a rare genetic disorder for which there are very few therapeutic options available. Free genetic testing
is provided to each patient through the International Pachyonychia Congenita Research Registry (IPCRR)
sponsored by the PC Project (www.pachyonychia.org) which is a non-profit USA public charity, supports
clinical and research activities related to the treatment of pachyonychia congenital. In India, we don’t have
such projects working on PC. With this case, we intend to draw attention to this condition and the role of
the dermatologist in the diagnosis.
What is new?
Pachyonychia congenita is a rare genodermatosis due to mutations in one of four keratin genes. To the
best of our knowledge this represents the first report of isolated PC with healthy other siblings and
parents.
Acknowledgement
We gratefully acknowledge the help of the Principal, PESIMSR, Kuppam and the professor and head of the
Department of DVL, PESIMSR, Kuppam.
Footnotes
Source of support: Nil
Conflict of Interest: Nil.
References
1. McLean WH, Hansen CD, Eliason MJ, Smith FJ. The phenotypic and molecular genetic features of
pachyonychia congenita. J Invest Dermatol. 2011;131:1015–7. [PubMed: 21430705]
2. Leachman SA, Kaspar RL, Fleckman P, Florell SR, Smith FJ, McLean WH, et al. Clinical and
pathological features of pachyonychia congenita. J Investig Dermatol Symp Proc. 2005;10:3–17.
3. Muller C. On the causes of congenital onychogryphosis. Mcn Med Wochenschr. 1904;49:2180–2.
4. Wilson AG. Three cases of hereditary hyperkeratosis of the nail bed. Br J Dermatol. 1905;17:13–4.
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5. Jadassohn J, Lewandowsky F. Jacob's Ikonographia Dermatologica. 1st ed. Berlin: Urban und
Schwarzenberg; 1906. Pachyonychia congenita. Keratosis disseminata circumscripta (follicularis).
Tylomata. Leukokeratosis linguae; pp. 29–31.
6. Al Aboud A, Al Aboud K. Josef Jadassohn (1863-1936), Felix Lewandowsky (1879-1921), and their
syndrome. Clin Cosmet Investig Dermatol. 2011;4:179–82. [PMCID: PMC3257882]
7. Ehsani A, Moeineddin F, Rajaee A. Pachyonychia congenita with woolly hair in a ten month old infant.
Indian J Dermatol Venereol Leprol. 2008;74:485–6. [PubMed: 19052410]
8. Johnson BL, Jr, Yan AC. Congenital diseases (Genodermatosis) In: Elder DE, editor. Lever's
Histopathology of the Skin. 10th ed. Philadelphia: Lippincott Williams and Wilkins; 2009. p. 138.
9. Balasubramanian S, Kaarthigeyan K, Ramnath B. Pachyonychia congenita with unusual features. Indian
Pediatr. 2009;46:897–9. [PubMed: 19887695]
10. Karen JK, Schaffer JV. Pachyonychia congenita associated with median rhomboid glossitis. Dermatol
Online J. 2007;13:21. [PubMed: 17511954]
11. Roche-Gamón E, Mahiques-Santos L, Vilata-Corell JJ. Paquioniquia congénita. Piel. 2006;21:72–8.
12. Rodríguez H, Cuestas G, Zanetta A, Balbarrey Z. Pachyonychia congenita with involvement of the
larynx. Acta Otorrinolaringol Esp. 2013;6519:264–6.
Figures and Tables
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Figure 1
Follicular keratotic papules over the face and shoulders
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Figure 2
Follicular papules over both shoulders and back upper chest
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Figure 3
Thickened, discolored and increased curvature of fingernails
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Figure 4
Sparing of palmar surface of both hands
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Figure 5
Thickened, discolored and increased curvature of toe nails
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Figure 6
Focal plantar keratoderma
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Figure 7
Oral leucokeratosis over tongue
Articles from Indian Journal of Dermatology are provided here courtesy of Medknow Publications
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Jadassohn Lewandowsky Syndrome: A Rare Entity

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