Embed Size (px)
Citation preview
Fax +41 61 306 12 34E-Mail [email protected]
Case Report
Dermatology 2008;217:181–186 DOI: 10.1159/000140678
Unilateral Spiny Hyperkeratosis
Case Report and Review of the Literature
Baruch Mevorah a Andrea Gat b Haim Golan a Sarah Brenner a
Departments of a Dermatology and b Pathology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine,Tel Aviv University, Tel Aviv , Israel
reports in the literature describing 59 cas-es with similar keratotic projections, with-out adnexal involvement [2–44] . These were variously characterized as punctate, filiform, spiny, digitate, acuminate, poro-keratotic or music box spine lesions. Such hyperkeratotic lesions have occurred ei-ther strictly on the palms and soles or, less often, in other body areas without palmo-plantar involvement. Here we use the term ‘spiny hyperkeratosis’ (SH) to include all such lesions regardless of location. Our re-view of the literature on such lesions is summarized in table 1 .
We describe a young man with lesions of SH limited to the left palm that appeared at the age of 2 years.
Case Report
A 33-year-old man complained of roughness of the palmar surface of the left hand that had begun at the age of 2 years. He attributed it to the growth of tiny skin projections in this area. Some of them would rub off during his work as a truck driver. He was never treated for this condi-tion and had taken no oral medication for many years. The patient’s parents, 5 sisters and 2 brothers as well as his 4 healthy chil-dren were not affected with a similar der-matosis.
At first glance the palmar surface of the left hand showed several ill-defined areas
Key Words
Spiny hyperkeratosis � Keratoderma � Palmoplantar keratoderma
Abstract
We describe the first case of unilateral spiny hyperkeratosis (SH) of the left hand, review the literature and discuss possible patho-mechanisms. SH can be sporadic or familial, often appearing in healthy individuals. How-ever, there is an association with various ma-lignancies in a significant number of the sporadic cases. Although there is no satis-factory explanation of this association, we agree with previous authors that a patient with SH appearing in adult life should be evaluated and followed for the presence of malignancy. Other patients with SH may suf-fer from a variety of nonmalignant diseases, which may be coincidental or causally relat-ed. SH is not a premalignant lesion of the skin and should not be confused with poro-keratosis which has a malignant potential. Except for excision of individual lesions, there is no permanent cure.
Copyright © 2008 S. Karger AG, Basel
Introduction
In 1967, Goldstein [1] reported a 32-year-old man with ‘multiple minute digi-tate hyperkeratoses’ on the chest, arms and legs. We were able to find 43 subsequent
Received: September 4, 2007 Accepted: December 11, 2007 Published online: June 24, 2008
Haim Golan, MD Department of Dermatology, Tel Aviv Sourasky Medical Center 6 Weizmann Street Tel Aviv 64239 (Israel) Tel. +972 3 697 3356, Fax +972 3 697 4810, E-Mail [email protected]
© 2008 S. Karger AG, Basel1018–8665/08/2172–0181$24.50/0
Accessible online at:www.karger.com/drm
with grayish dots on the volar extremities of the fingers and the thenar eminence ( fig. 1 ). On closer examination, these gray-ish dots appeared as minuscule spiny or hair-like projections ( fig. 2 ). There wereno lesions anywhere else on the body. The general physical examination was noncon-tributory. The patient refused to give blood for laboratory tests and was lost to follow-up.
Histopathology A biopsy of a tiny keratotic projection
on the left palm showed a depressed area with thin epidermis, hypogranulosis and a spike-like orthoparakeratotic column with light eosinophilic staining above it ( fig. 3 ). Dyskeratotic cells were not ob-served. There was a perinuclear halo in some of the keratinocytes, but there was no intracytoplasmic edema. The sur-rounding epidermis appeared normal with an unremarkable keratin layer ( fig. 4 ).
Discussion
SH may be sporadic or hereditary ( ta-ble 1 ). The median age of onset in patients with only palmoplantar involvement is 59 years (range 2–81 years), while in those without palmoplantar involvement it is 31 years (range 15–71 years). SH is a chronic dermatosis and may last for years; the me-
Mevorah /Gat /Golan /Brenner Dermatology 2008;217:181–186182
dian duration at the time of examination is 7 years for patients with only palmo-plantar involvement and 8 years for those without such involvement. Exceptionally, the course of SH may be intermittent with spontaneous regressions and recurrences [18, 38] .
The tiny keratotic projections usually resemble the spines of a music box [27] and
are firmly attached to the surrounding normal skin. In 1 case, although most le-sions were spiny, a few were flat-topped or dome-shaped keratotic papules [12] . In 2 patients [26, 29] , the keratotic spines pro-truded from tiny erythematous papules. SH is usually asymptomatic, but there may be slight pain on pressure or mild pruritus. Patients may complain of a feeling of sand
paper or of being embarrassed when shak-ing hands.
Histologically, the spiny projections arise from the interadnexal epidermis. They resemble the cornoid lamella of po-rokeratosis [45] . They are parakeratotic on the palms and soles and usually orthoker-atotic or paraorthokeratotic on other body sites. The epidermis tends to be indented
Fig. 1. Dark dots in left thenar region. Fig. 2. Closer view of left thenar region showing minuscule spiny hyperkeratoses.
Fig. 3. Depressed area with thin epidermis, hypogranulosis anda spike-like orthoparakeratotic column above it. The column stands out with a slight eosinophilic staining. Hematoxylin-eosin. ! 4.
Fig. 4. Higher magnification of the area shown in figure 3. There is no dyskeratosis. In some of the keratinocytes, a perinuclear halo is present but there is no intracytoplasmic edema. The surround-ing epidermis is normal with an unremarkable keratin layer. He-matoxylin-eosin. ! 10.
Unilateral Spiny Hyperkeratosis Dermatology 2008;217:181–186 183
with a thinned or absent granular layer under the parakeratotic spines and nor-mal or even thickened under orthokera-totic projections. There are no significant changes in the epidermis surrounding the spines, and the superficial dermis may show a slight mononuclear cell infiltrate. Several studies have shown different elec-tron microscopy results [13, 19, 34] .
The following have been suggested in the differential diagnosis of SH depending on whether lesions are palmoplantar or situated elsewhere: punctate palmoplantar porokeratosis, punctate palmoplantar ker-atoderma, keratosis punctata of palmar creases, viral warts, arsenical keratoses, li-chen nitidus, acanthosis nigricans, hyper-keratosis lenticularis perstans [7, 15, 22, 27, 30, 39] . All of these are clinically or histo-logically different from SH. For instance, the lesions in punctate palmoplantar kera-toderma appear as verruca- or clavus-like papules that are depressed and contain a central horny plug [22, 27] . While some of the lesions in punctate porokeratosis of the palms and soles may be spiny, there arealways underlying keratinocyte changes such as vacuolization and dyskeratosis. Many authors have pointed out that such keratinocyte changes do not exist under the cornoid lamella-like spines of SH [15, 19, 20, 22, 27, 33, 34] . Therefore, the label-ing of SH as porokeratotic in some of the reports is misleading [2, 13, 16, 19, 26, 44] .
It is important to differentiate SH fromporokeratosis because the latter, unlike SH, is premalignant.
There are other dermatoses with kera-totic spines that are rarely mentioned in the differential diagnosis of SH. Multi-ple myeloma may be accompanied by fol-licular or nonfollicular keratotic spicules, which can be generalized or predominant on the face and scalp [29, 40] . Keratosis-pilaris-spinulosa-like lesions have been re-ported in paraneoplastic syndromes [47] . Finally, the recently recognized tricho-dysplasia of immunosuppression presents with follicular spiny projections [48] .
SH, whether on the palms and soles or elsewhere, is often associated with malig-nancies ( table 1 ). There is no significant difference in the incidence of cancers be-tween patients with palmoplantar SH and those with SH in other areas (Fisher’s exact tests, p value = 0.77). SH of the palms and soles may appear either when the malig-nancy is diagnosed, a few years before or even many years prior to this diagnosis ( ta-ble 2 ). Table 3 shows 6 cases of nonpalmo-plantar SH associated with malignancies: 4 patients with breast cancer, 1 with ovar-ian cancer and 1 with cancer of the larynx. SH appeared after the diagnosis of malig-nancy in all of them. Interestingly, lesions of SH were confined to the field of post-mastectomy irradiation, and widespread but absent from the field of irradiation in
the case with ovarian cancer. This may suggest that irradiation in combination with breast cancer may be a triggeringfactor.
One textbook [48] gives 5 criteria (Curth’s postulates) to associate a derma-tosis and malignancy: (1) concurrent on-set, (2) parallel course, (3) uniform site or type of neoplasm, (4) statistical association and (5) genetic linkage. The data on the re-viewed cases of SH and malignancies only partially satisfy these criteria. There is a high incidence of malignancy in patients with SH ( table 1 ), and a good number of cases satisfy criterion 1 ( table 2 ). However, SH disappeared after removal of the can-cer in only 1 case [6] (parallel course). Fur-thermore, there was a significant variety of cancers in the reported cases ( table 1 ). No genetic linkage or an explanation of this association has been reported. Despite these discrepancies and because of the high incidence of cancers ( table 1 ), we agree with most previous authors that one should look for malignancy in a patient with SH. As mentioned above, our patient was not cooperative, and we could not fol-low him for the possible development of internal malignancy.
Various nonmalignant diseases have been reported in patients with SH ( table 1 ). Although some of these associations were probably coincidental, others could have been a triggering factor in the appearance
Table 1. SH – summary of the literature
Site of keratoticprojections
Cases Heredity Systemicor skincancer
Site or type of cancer Associations in patients without cancer Withoutassocia-tions
Palms-soles withoutother areas [3, 4, 16–19, 22–28,30–41, 43, 44]
38 7 (19%) 13 (34%) Rectosigmoid (n = 3), bronchus(n = 2), kidney (n = 1), breast (n = 1), malignant melanoma (n = 1),lymphoid leukemia (n = 1), liver (n = 1), esophagus (n = 1), squamous cell cancer of skin (n = 1), squamous cell cancer of gingival mucosa (n = 1)
13 patients (34%): myelofibrosis, diabetes, Darier’s disease, polycystic kidneys, hyperlipidemia, cardiovascular disease, asthma, peptic ulcer, gout,sebaceous hyperplasia, CNS disease,pulmonary tuberculosis, kidney infection
11 (29%)
Palms-soles andother areas [21]
1 – – – – 1
Other areas withoutpalms-soles [1, 2,5–7, 9–12, 15, 20,21, 24, 29, 42]
21 6 (28%) 6 (28%) Breast (n = 4), ovary (n = 1),larynx (n = 1)
7 patients (33%): kidney infection,renal insufficiency, female pattern hair+ increased sella turcica, diabetes, cardiovascular disease, anemia,Crohn’s disease, vocal cord polyp,monoclonal gammopathy, peptic ulcer, disseminated superficial actinic porokeratosis
8 (38%)
Mevorah /Gat /Golan /Brenner Dermatology 2008;217:181–186184
of lesions. An example is the report of a 50-year-old man who developed pulmonary tuberculosis and palmar SH simultane-ously [28] . Under treatment, tuberculosis improved and SH regressed spontaneous-ly. In another report [42] , a 55-year-old man presented with disseminated superfi-cial actinic porokeratosis (DSAP). Within 2 months of oral etretinate, DSAP mark-edly improved but SH appeared at the edge of previous DSAP lesions. Three months after stopping the retinoid, DSAP recurred but SH disappeared. Table 1 also shows that SH may appear in healthy individuals without other anomalies.
There have been several attempts to elucidate the pathomechanism of SH. In one study [19] , using autoradiography the authors showed that only basal cells under the palmoplantar keratotic spines were stimulated to proliferate, and not cells of sweat units. They also identified keratins 6 and 16 in the keratotic projections, which
are markers of hyperproliferating cells, ex-plaining the parakeratosis in the lesions. In another report [34] on 6 cases with pal-moplantar SH, the authors cited electron microscope and animal studies to suggest that SH was possibly related to treatment with simvastatin (a 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor) taken by some of their patients for hyper-cholesterolemia. The same group of re-searchers analyzed these 6 cases with hair-specific antikeratin antibodies and by electron microscopy [50] and suggested that SH represented an ectopic hair forma-tion on the palms and soles in their pa-tients.
Based on a recent discussion on inter-adnexal epidermal stem cells [45] it would seem that the etiological factor(s) of SH must act, first of all, on the epidermal proliferative unit(s) (EPU) underlying the spiny keratotic projections. An interad-nexal self-renewing EPU is comprised of
a column of cells at the base of which there is a single stem cell and a few basal keratinocytes [45] . An environmental change such as treatment with simva-statin for hypercholesterolemia [34] or treatment with a retinoid for DSAP [42] would activate the EPU into hyperprolif-eration giving rise to SH. In other cases, a genetic mutation in the stem cell or its im-mediate progeny within EPUs could be the cause of epidermal hyperproliferation and the resultant SH. Our patient could be such a case. He was apparently in good health and was under no medication. A somatic mutation could have occurred in interadnexal EPUs of his left palm at the age of 2 years.
Topical agents containing salicylic acid, urea, lactic acid, steroids or tretinoin have been unsuccessful therapeutic agents. However, application of preparations con-taining the following substances has given good results: 5% 5-fluorouracil [22] , 6%
Table 2. SH of the palms and soles: association with malignancy
Ref. No. Type of malignancy SH appears before or at timeof diagnosis of the malignancy
Status of SH after treatment of malignancy
8 kidney tumor not mentioned not mentioned14 rectosigmoid cancer at time no regression 3 months after surgery18 breast cancer many years before evolution by remissions and flares25 rectum cancer many years before no regression 3 years after surgery26 bronchial cancer at time insufficient data30 malignant melanoma at time no regression 6 months after surgery32 sigmoid cancer at time no regression 6 months after surgery35 lymphoid leukemia many years before no regression despite oncotherapy
3 bronchial cancer several years before no regression 3 months after surgery39 liver cancer 1 year before insufficient data36 esophageal tumor not mentioned insufficient data34 cutaneous squamous cell cancer not mentioned all lesions punch biopsied, no recurrence41 gingival squamous cell cancer at time insufficient data
Table 3. SH in areas other than palms and soles: association with malignancy
Ref. No. Areas with SH Type of cancer SH appears after diagnosis of malignancy Remarks
9 lesions limited to irradiation field breast 2 years after postmastectomy irradiation1 SH strictly limited to irradiation field21 back, all extremities ovary 16 years after postsurgery irradiation no lesions of SH in irradiation field11 lesions limited to irradiation field breast shortly after postmastectomy irradiation1 SH confined to area of irradiation
lesions limited to irradiation field breast shortly after postmastectomy irradiation1 SH confined to area of irradiationlesions limited to irradiation field breast shortly after postmastectomy irradiation1 SH confined to area of irradiation
6 ears, chest, all extremities larynx 2 years after diagnosis of cancer SH disappears 11 weeks after surgery
1 Irradiation may have been a triggering factor after mastectomy.
Unilateral Spiny Hyperkeratosis Dermatology 2008;217:181–186 185
salicylic acid gel under occlusion [27] , 12% ammonium lactate [34] and 0.002% tacal-citol [41] . Unfortunately, lesions recurred after discontinuation of treatment. In 1 case, SH disappeared under oral retinoids [21] , but there was no information on le-
sion status after stopping medication. Only when keratotic projections were re-moved by excision was the result perma-nent [34] .
In conclusion, SH can be sporadic or familial, often appearing in healthy indi-
viduals. SH can also be a marker of a pre-disposition to develop various malignan-cies or appear in association with a num-ber of nonmalignant diseases. The latter are coincidental or may be causally related to SH [28] .
References
1 Goldstein N: Multiple minute digitate hy-perkeratoses. Arch Dermatol 1967; 96: 692–693.
2 Aufgang A: Hyperkératose piliforme dis-séminée familiale. Ann Dermatol Syphiligr (Paris) 1972; 99: 381–390.
3 Herman PS: Punctate porokeratotic kerato-derma. Dermatologica 1973; 147: 206–213.
4 Schiff BL, Hughes D: Palmoplantar keratosis acuminata with facial sebaceous hyperpla-sia. Arch Dermatol 1974; 109: 86–87.
5 Yoon SW, Gibbs RB: Multiple minute digi-tate hyperkeratoses. Arch Dermatol 1975; 111: 1176–1177.
6 Ferrandiz C, Savall R, Baumann E: Hiper-queratosis multiple minuta y digita: un sín-toma paraneoplásico? Med Cutan Ibero Lat Am 1978; 5–6: 279–283.
7 Frenk E, Mevorah B, Leu F: Disseminated spiked hyperkeratosis: an unusual discrete nonfollicular keratinization disorder. Arch Dermatol 1981; 117: 412–414.
8 Beylot C, Taieb A, Bioulac P, Doutre MS, Foix P: Hyperkératose palmo-plantaire fili-forme et néoplasie viscérale. Ann Dermatol Vénéréol 1982; 109: 747–748.
9 Burns DA: Post-irradiation digitate kerato-ses. Clin Exp Dermatol 1986; 11: 646–649.
10 Nedwich JA, Sullivan JJ: Disseminated spiked hyperkeratosis. Int J Dermatol 1987; 26: 358–361.
11 Vestey JP, Hunter JA: Post-irradiation digi-tate keratoses. Clin Exp Dermatol 1987; 12: 315–316.
12 Balus L, Donati P, Amantea A, Breathnach AS: Multiple minute digitate hyperkeratosis. J Am Acad Dermatol 1988; 18: 431–436.
13 Friedman SJ, Herman PS, Pittelkow MR, Su D: Punctuate porokeratotic keratoderma. Arch Dermatol 1988; 124: 1678–1682.
14 Fegueux S, Bilet S, Crickx B, Perron J, Gros-sin M, Belaich S: Hyperkératose palmo-plan-taire filiforme et cancer rectosigmoïdien. Ann Dermatol Vénéréol 1988; 115: 1145–1146.
15 Aloi FG, Molinero A, Pippione M: Parakera-totic horns in a patient with Crohn’s disease. Clin Exp Dermatol 1989; 14: 79–81.
16 Lestringant GG, Berge T: Porokeratosis punctata palmaris et plantaris: a new entity? Arch Dermatol 1989; 125: 816–819.
17 Knobler EH, Grossman ME, Rabinowitz AD: Multiple minute palmar-plantar digi-tate hyperkeratoses. Br J Dermatol 1989; 121: 239–242.
18 Hillion B, Le Bozec P, Moulonguet-MichauI, Blanchet-Bardon C, Petit A, Stephan J, Civatte J: Hyperkératose palmo-plantaire fi-liforme et cancer du sein. Ann Dermatol Vé-néréol 1990; 117: 834–836.
19 Kondo S, Shimoura T, Hozumi Y, Aso K: Punctate porokeratotic keratoderma: some pathogenetic analyses of hyperproliferation and parakeratosis. Acta Derm Venereol (Stockh) 1990; 70: 478–482.
20 Vaillant L, de Muret A, Arbeille B, Morere JP, Muller CH, Lorette G: Hyperkératose fili-forme diffuse. Ann Dermatol Vénéréol 1991; 118: 891–894.
21 Moulonguet-Michau I, Bazex J, Franck N, Alibert M, Blanchet-Bardon C, Civatte J, Du-bertret L: Hyperkératoses multiples minus-cules. Ann Dermatol Vénéréol 1991; 118: 615–618.
22 Osman Y, Daly TJ, Don PC: Spiny keratoder-ma of the palms and soles. J Am Acad Der-matol 1992; 26: 879–881.
23 Zarour H, Grob JJ, Andrac L, Bonerandi JJ: Palmoplantar orthokeratotic filiform hyper-keratosis in a patient with associated Darier’s disease: classification of filiform hyperkera-tosis. Dermatology 1992; 185: 205–209.
24 Feldmann R, Harms M: Multiple filifor-me Hyperkeratosen. Hautarzt 1993; 44: 658–661.
25 LeGuyadec T, Beaulieu PH, Darie H, Four-nier B, Gros PH, Millet P: Hyperkératose palmaire filiforme orthokératosique: un nouveau cas associé à un cancer rectal.Ann Dermatol Vénéréol 1994;S123: 91–92.
26 Bianchi L, Orlandi A, Iraci S, Spagnoli LG, Nini G: Punctate porokeratotic keratoder-ma – its occurrence with internal neoplasia. Clin Exp Dermatol 1994; 19: 139–141.
27 McGovern TW, Gentry RH: Spiny kerato-derma: case report, classification, and treat-ment of music box spine dermatoses. Cutis 1994; 54: 389–394.
28 Gimenez-Arnau A, Camarasa JG: Palmar fi-liform or spiny hyperkeratosis associated with pulmonary tuberculosis. J Eur Acad Dermatol Venereol 1994; 3: 400–406.
29 Paul C, Fermand JP, Flageul B, Caux F, Duterque M, Dubertret L, Aractingi S: Hy-perkeratotic spicules and monoclonal gam-mopathy. J Am Acad Dermatol 1995; 33: 346–351.
30 Kaddu S, Soyer HP, Kerl H: Palmar filiform hyperkeratosis: a new paraneoplastic syn-drome? J Am Acad Dermatol 1995; 33: 337–340.
31 Anderson D, Cohen DE, Lee HS, Thellman CH: Spiny keratoderma in association with autosomal dominant polycystic kidney dis-ease with liver cysts. J Am Acad Dermatol 1996; 34: 935–936.
32 Rault S, Salmon-Ehr V, Cambie MP, Armin-gaud P, Barhoum K, Ploton D, Kalis B: Hy-perkératose palmo-plantaire filiforme para-kératosique et adénocarcinome digestif. Ann Dermatol Vénéréol 1997; 124: 707–709.
33 Urbani CE, Moneghini L: Palmar spiny ker-atoderma associated with type IV hyperlipo-proteinemia. J Eur Acad Dermatol Venereol 1998; 10: 262–266.
34 Horton SL, Hashimoto K, Toi Y, Miner JE, Mehregan D, Fligiel A, Savoy LB, Aronson P: Spiny keratoderma: a common under-re-ported dermatosis. J Dermatol 1998; 25: 353–361.
35 Bernal AI, González A, Aragoneses H, Mar-tinez G, Garcia M: A patient with spiny kera-toderma of the palms and a lymphoprolifer-ative syndrome: an unrelated paraneoplastic condition? Dermatology 2000; 201: 379–380.
36 Handa Y, Sakakibara A, Araki M, Yamana-ka N: Spiny keratoderma of the palms and soles – report of two cases. Eur J Dermatol 2000; 10: 542–545.
37 Mehta RK, Mallett RB, Green C, Rytina E: Palmar filiform hyperkeratosis (FH) associ-ated with underlying pathology? Clin Exp Dermatol 2002; 27: 216–219.
38 Guhl G, Goiriz R, Vargas E, Fraga J, Garcia-Diez A, Fernandez-Herrera J: Queratoder-mia espinosa palmar: a propósito de un caso. Actas Dermosifiliogr 2005; 96: 392–394.
39 Blanes M, Carnicer F, Botella R, Pastor N, Peiro FM: Filiform horny projections on the palms of a 69-year-old man – quiz case. Arch Dermatol 2006; 142: 235–240.
40 Bachmeyer C, Émilie S, Moguelet P: Hyper-kératose filiforme palmo-plantaire. Ann Dermatol Vénéréol 2006; 133: 827–828.
Mevorah /Gat /Golan /Brenner Dermatology 2008;217:181–186186
41 Yukawa M, Satoh T, Higuchi T, Yokozeki H: Spiny keratoderma of the palms successfully treated with topical tacalcitol. Acta Derm Venereol 2007; 87: 172–174.
42 Carmichael AJ, Tan CY: Digital keratosis – a complication of etretinate used in the treat-ment of disseminated superficial actinic po-rokeratosis. Clin Exp Dermatol 1990; 15: 370–371.
43 Perez-Perez L, Peteiro C, Canchez-Aguilar D, Toribio J: Palmar filiform parakeratotic hyperkeratosis without underlying malig-nancy. Actas Dermosifiliogr 2007; 98: 420–424.
44 Erkek E, Atasoy P: Fluorescence of heredi-tary type II punctate porokeratotic kerato-derma (spiny keratoderma) with a Wood’s light: stars under the moonlight. J Am Acad Dermatol 2007; 57: 563–564.
45 Wade TR, Ackerman AB: Cornoid lamella-tion: a histologic reaction pattern. Am J Der-matopathol 1980; 2: 5–15.
46 Nazzaro P, Argentieri R, Balus L, Bassetti F, Fazio M, Giacalone B, Ponno R: Syndrome paranéoplasique avec lésions papulo-kérato-siques des extrémités et kératose pilaire spi-nulosique diffuse. Ann Dermatol Syphiligr (Paris) 1974; 101: 411–413.
47 Campbell RM, Ney A, Gohh R, Robinson-Bostom L: Spiny hyperkeratotic projections on the face and extremities of a kidney trans-plant recipient. Arch Dermatol 2006; 142: 1643–1648.
48 Callen JP: Dermatologic signs of systemic diseases; in Bolognia JL, Jorizzo JL, Rapini RP, et al (eds): Dermatology, ed 1. London, Mosby, 2003, vol 1, pp 712–713.
49 Hashimoto K, Toi Y, Horton S, Sun TT: Spiny keratoderma – a demonstration of hair kera-tin and hair type keratinization. J Cutan Pathol 1999; 26: 25–30.
50 Kaur P: Interfollicular epidermal stem cells: identification, challenges, potential. J Invest Dermatol 2006; 126: 1450–1458.
