BJD

C L I N I C A L A N D L A B O R A T O R Y I N V E S TI G A T I O N S British Journal of Dermatology

Psoriasis and melanocytic naevi: does the first confer a

protective role against melanocyte progression to naevi?
N. Balato, L. Di Costanzo, A. Balato, C. Patruno, M. Scalvenzi and F. Ayala
Sezione di Dermatologia Clinica, Allergologica e Venereologica, Dipartimento di Patologia Sistematica, Università di Napoli Federico II, 80131 Naples, Italy

Summary

Correspondence Background Some of the cytokines that have effects on melanogenesis are also
Luisa Di Costanzo. reported to be involved in psoriasis.
E-mail: luisadicostanzo@virgilio.it Objectives We therefore studied the relationship between psoriasis and melanocytic
naevi. In particular, the aim of our study was to investigate the number of
Accepted for publication
13 February 2011
melanocytic naevi in patients with psoriasis vs. controls.
Methods We performed a prospective case–control study, analysing 93 adult
Funding sources patients with psoriasis and 174 adult aged-matched controls. For each participant
None. a questionnaire was completed to establish personal data, personal medical his-
tory, and personal and familial history of skin cancer and psoriasis. We analysed
Conflicts of interest
interleukin (IL)-1a, IL-6 and tumour necrosis factor (TNF)-a gene expression at
None declared.
the peripheral blood mononuclear cell level in patients with psoriasis and in
DOI 10.1111/j.1365-2133.2011.10271.x controls.
Results In our study, patients with psoriasis presented a lower number of areas
with naevi in comparison with controls (P < 0Æ0001). Nobody had ever had
squamous cell carcinoma or melanoma in the psoriatic group; moreover, there
was a significant difference in familial history of melanoma between the two
groups (none in the psoriatic group vs. 8% in the control group; P < 0Æ05).
IL-1a, IL-6 and TNF-a expression levels were higher in patients with psoriasis.
Conclusions People with psoriasis had fewer melanocytic naevi. This suggests that
the proinflammatory cytokine network in psoriasis skin might inhibit melanogen-
esis, melanocyte growth and ⁄or progression to naevi.

Psoriasis is a common skin disease that affects about 2–3% of
white people.1 It is an organ-specific autoimmune disease that
is triggered by an activated cellular immune system and with
similarity to other immune-mediated diseases such as Crohn
disease, rheumatoid arthritis, multiple sclerosis and juvenile-
onset diabetes.1–7 Psoriasis is characterized by excessive
growth and aberrant terminal differentiation of keratinocytes
that cause the surface scale in psoriatic plaques.7 The disease is
considered to be a genetically programmed disease of dysregu-
lated inflammation, which is driven and maintained by multi-
ple components of the immune system. The pathological
balance between innate immunity (mediated by natural killer
cells and natural killer T lymphocytes) and acquired immunity
(mediated by T lymphocytes) results in the production of
cytokines, chemokines and growth factors that contribute to
the inflammatory infiltrate seen in psoriatic plaques.6 Two
fundamentally different cell types interact in the formation of
a psoriatic lesion: epidermal keratinocytes and mononuclear
leucocytes.6 Psoriasis lesional skin shows a prominent presence
of inflammatory cells localized both in the papillary dermis
and in the epidermis.8 Psoriasis is generally thought to be a
type 1 T-cell disease because interfereron (IFN)-c-producing T
cells predominate in lesional skin and in the peripheral circu-
lation; moreover, type 1 response-sustaining mechanisms are
locally present. T-helper (Th)17 and Th22 cells are also
detected in psoriatic skin lesions.7 Type 1 cytokines, repre-
sented mainly by IFN-c, are locally produced by infiltrating
Th1, T-cytotoxic 1 and natural killer cells, and are responsible
for the activation of resident skin cells, in particular keratino-
cytes.7,8 Because of their intrinsic defects, psoriatic keratino-
cytes respond aberrantly to cytokines and show altered
intracellular signalling pathways. The uncontrolled hyper-
proliferation and differentiation observed in psoriatic skin
could derive from a dysregulated production of tissue growth
factors and regulators.9
Keratinocyte-derived cytokines such as platelet-derived
growth factor and vascular endothelial growth factor influence
the growth of supporting stromal cells. Activated stromal cells
overproduce factors such as keratinocyte growth factor (KGF)
that can induce proliferation of keratinocytes. Many immune-

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1262 BJD  2011 British Association of Dermatologists 2011 164, pp1262–1270

derived cytokines, including interleukin (IL)-1, IL-6, IL-17,
IL-19, IL-20, IL-22, tumour necrosis factor (TNF)-a and IFNs,
can also regulate keratinocyte proliferation, with some
immune-derived cytokines clearly serving as alternative mito-
gens for this cell type.7,10 The inflammatory cytokine milieu
also influences the immune functions of fibroblasts and endo-
thelium, with the latter being critical for leucocyte trafficking
and extravasation.8 It has been demonstrated that keratinocytes
synthesize and secrete many cytokines; some of these interact
with other skin cells like melanocytes.11
These cells reside along the basal layer of epidermis, closely
associated with both keratinocytes and Langerhans cells. They
produce melanin by the melanogenesis complex pathway. The
synthesis and distribution of melanin in the epidermis depend
on several steps: transcription of melanogenic proteins, mela-
nosome biogenesis, sorting of melanogenic proteins into the
melanosomes, transport of melanosomes to the tips of mela-
nocyte dendrites and finally transfer into keratinocytes, where
they form a melanin cap over the nuclei to protect DNA from
ultraviolet (UV) damage. These events are tightly regulated by
a variety of paracrine and autocrine factors in response to
endogenous and exogenous influences, principally UV irradia-
tion.12 Two types of melanins are synthesized within melano-
somes: eumelanin and phaeomelanin. Both are derived
products of 3,4-dihydroxyphenylalanine (DOPA) and both are
formed in melanosomes from tyrosine through a series of oxi-
dative steps. The melanin synthesis requires the enzyme tyrosi-
nase and tyrosinase-related proteins (TRP-1 and TRP-2) that
catalyse the oxidation of tyrosine to L-DOPA; this reaction is
involved in formation of benign melanocytic naevi and in
abnormal accumulation of melanin pigments.12–14
It is well known that several skin cell types, including kerat-
inocytes, play a strong secretory activity, giving rise to chemi-
cal messengers that may control the proliferation and
differentiation of melanocytes and the rate of melanin produc-
tion. These factors can act alone or synergistically. The main
factors are represented by a-melanocyte stimulating hormone
(MSH), adrenocorticotropic hormone (ACTH), endothelin-1
(ET-1) and many other inflammatory and growth media-
tors.12,15–18 a-MSH and ACTH are potent stimulators of mela-
nogenesis through proopiomelanocortin (POMC) precursor
and derived peptides. The latter are synthesized also by epider-
mal keratinocytes, as well as by the pituitary gland. UV irradi-
ation and several cytokines induce POMC expression in
keratinocytes.15 Systemic administration of a-MSH, b-MSH,
ACTH or a-MSH analogues increases skin pigmentation pre-
dominantly in sun-exposed areas.12 ET-1 is also involved in
the regulation of melanogenesis, through activation of tyrosi-
nase, increasing TRP-1 levels and stimulatiing melanocyte pro-
liferation and dendrite formation.12,16
Several inflammatory mediators can affect skin pigmenta-
tion. Prostaglandins PGE2 and PGF2a and leukotrienes, lipid
compounds derived from arachidonic acid, are mediators of
inflammatory responses that affect melanocyte function. Their
level is elevated in sunburned skin and in a variety of inflam-
matory dermatoses.12,17 KGF, a member of the fibroblast
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BJD  2011 British Association of Dermatologists 2011 164, pp1262–1270
Psoriasis and melanocytic naevi, N. Balato et al. 1263
growth factor family, has been shown to promote melano-
some transfer from melanocytes to keratinocytes.12,18 There is
evidence to suggest the existence of endogenous melanogenic
inhibitors. Swope et al. first hypothesized and demonstrated
that some epidermal cytokines (IL-1a, IL-6 and TNF-a) may
provide autocrine and paracrine regulatory inhibition signals
for melanocytes. In fact, these cytokines could downregulate
melanization and replication of melanocytes by a greater
inhibitory effect on tyrosinase activity.11 Such a hypopigment-
ing effect has been demonstrated also for transforming growth
factor (TGF)-b1 using B16 ⁄F10 mouse melanoma cells as a
model. The inhibitory effect of TGF-b1 involves decreases in
the intracellular levels of tyrosinase and TRP-1, without
changes in TRP-2 activity.14,19 Table 1 summarizes the role of
these factors in melanogenesis and psoriasis. Some of these
cytokines that have effects on melanogenesis are reported to
be involved in a variety of normal or pathological conditions
such as wound healing, exposure to UV radiation or contact
irritants and psoriasis.14,19 Therefore, the possible immuno-
logical interaction between psoriasis and melanogenesis is par-
ticularly interesting for clinical and therapeutic implications.
There is some evidence that immunosuppressive therapy is as-
sociated with the development of eruptive benign melanocytic
naevi and acquired dermal melanocytosis.20–23 As some cyto-
kines involved in psoriasis pathogenesis could play a role in
melanocyte growth, the aim of our study was to investigate
the relationship between psoriasis and melanocytic naevi.
Patients and methods
This study was approved by the ethics committee of the
School of Medicine, University of Naples Federico II and was
carried out during winter and spring seasons (January–June)
2010 in our Dermatological Clinic. We performed a prospec-
Table 1 Effect of paracrine factors on melanogenesis and psoriasis
pathogenesis
Effect on Effect on psoriasis
Factor melanogenesis pathogenesis
a-MSH › ›
ACTH › ›
ET-1 › ›
PGE2 and PGF2a › fl
b-FGF › ›
KGF › ›
IL-1a fl ›
IL-6 fl ›
TNF-a fl ›
TGF-b1 fl ›
a-MSH, a-melanocyte stimulating hormone; ACTH, adrenocorti-
cotropic hormone; ET-1, endothelin-1; PG, prostaglandin;
b-FGF, basic fibroblast growth factor; KGF, keratinocyte growth
factor; IL, interleukin; TNF, tumour necrosis factor; TGF,
transforming growth factor.
1264 Psoriasis and melanocytic naevi, N. Balato et al.

tive case–control study, analysing a group comprising 93 adult well-circumscribed brown flat or raised lesions with a distinct
patients with psoriasis (psoriasis group – PG; age range 18– border and a diameter of 2 mm or larger (measured by over-
85 years) and 174 adult aged-matched controls (control group laying a 2-mm stencil of a circle).
– CG; age range 18–84 years). Table 2 summarizes character- The regional distribution of naevi was recorded using a sche-
istics of each group in terms of age and gender. It summarizes matic body chart divided into 16 areas (A–P; Appendix 1); the
also, for PG, the psoriasis medical history in terms of age at number of naevi was registered separately in each area using five
onset, Psoriasis Area and Severity Index (PASI) on day of ranges (0 naevi; < 10 naevi; 11–30 naevi; 31–50 naevi; > 50
examination and psoriasis therapy. Controls comprised consec- naevi) and the total number of areas with naevi was also
utive patients attending our ambulatory service who fulfilled counted. Lesions identified as congenital melanocytic naevi and
the study inclusion criteria. In PG, inclusion criteria included atypical melanocytic naevi were checked separately. The pres-
subjects affected by psoriasis or arthritic psoriasis undergoing ence of congenital naevi was defined on anamnestic (when the
treatment with topical products, acitretin and narrowband mole was known to have been present since birth or was
UVB alone or in combination. In PG and CG, exclusion criteria detected before 2 years of age by the parents)25 and dermoscop-
included subjects undergoing treatment with immunosuppres- ic features (presence of specific dermoscopic characteristics of
sant therapy including systemic corticosteroids, ciclosporin, congenital melanocytic naevi, defined by Changchien et al.25).
methotrexate, psoralen plus UVA (PUVA) therapy and biologic Diagnosis of atypical naevi was made clinically and dermoscopi-
drugs, patients affected by other inflammatory skin diseases, cally. Dermoscopic examination was performed by using the
or patients who had already received a diagnosis of atypical brightest pocket dermatoscope, DermLite II PRO HR (3 Gen
melanocytic naevi. A written consent form was required to LLC, Dana Point, CA, U.S.A.); lesions were diagnosed following
participate in the study. For each participant, a questionnaire the seven-point checklist classification.26 Before the examina-
(Appendix 1) was administered by the same experienced der- tion, topical petrolatum containing 10% salicylic acid was
matologist to establish (i) personal data; (ii) personal medical administered to all psoriatic subjects for 2 weeks in order to
history including presence of atopy (defined as the presence prevent the covering of naevi by psoriasis plaques.
of at least one of atopic dermatitis, allergic rhinoconjunctivitis
or bronchial asthma); (iii) medical history of skin cancer
Blood samples
including melanoma; and (iv) psoriasis. Familial history for
skin cancer and psoriasis was also recorded. The study population included 14 patients in PG and 14
The following phenotype ⁄clinical characteristics were patients in CG; subjects were distributed by naevi ranges and
reported in the questionnaire: PG: PASI on day of examina- were matched for sex and age. Patients did not receive any
tion; and PG and CG: skin phototype (Fitzpatrick skin types24 systemic treatment for psoriasis for at least 1 month before
were used for categorization); presence of facial freckles; and blood sampling. Blood from patients and controls was
number of melanocytic naevi in all body areas, defined as all obtained by venepuncture and collected in sterile heparinized
glass vials. Peripheral blood mononuclear cells (PBMC) were
Table 2 Study population separated by density-gradient centrifugation over Ficoll-Paque
PLUS (GE Healthcare Bio-Sciences AB, Uppsala, Sweden). Total
Psoriasis Control RNA was isolated from 5 · 106 PBMC by RNeasy Mini Proto-
group group
col (Qiagen, Valencia, CA, U.S.A.) and cDNA was prepared
(n = 93) (n = 174)
(Transcriptor High Fidelity cDNA Synthesis; Roche, Indiana-
Sex, n (%) polis, IN, U.S.A.) according to the manufacturer’s instructions.
Male 48 (52) 60 (34Æ5)
Quantitative reverse transcription-polymerase chain reaction
Female 45 (48) 114 (65Æ5)
Age (years), mean (range) 46 (18–85) 42 (18–84) (PCR) (LightCycler; Roche) was used to analyse levels of
Age at onset (years), n (%) expression of TNF-a, IL-6 and IL-1a. PCR primers for the
1–10 53 (57) selected genes were designed based on published sequences,
11–20 22 (24) and their specificity was verified with BLAST alignment search.
21–30 15 (16) To confirm amplification of the expected size fragment, ampli-
31–40 1 (1) fication products were characterized by agarose gel electropho-
41–50 2 (2)
resis. Melting curve analysis was carried out after completion
PASI, n (%)
< 10 51 (55) to confirm the presence of single amplified species. Relative
‡ 10 42 (45) mRNA levels were determined by the comparative threshold
Psoriasis therapy, n (%) cycle method, and their expression was normalized to the
Topical drugs 64 (69) expression of 18S mRNA.
NB-UVB 22 (24)
Acitretin 7 (8)
Statistical analysis
PASI, Psoriasis Area and Severity Index; NB-UVB, narrowband
ultraviolet B. Data were described statistically in terms of mean, frequencies
and percentages when appropriate. Comparisons between

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BJD  2011 British Association of Dermatologists 2011 164, pp1262–1270

groups were done using v2 test and Fisher’s exact test for
qualitative variables. Statistical analyses were performed using
a software package (SPSS version 15.0 for Windows; SPSS Inc.,
Chicago, IL, U.S.A.). Gene expression analysis at PBMC level
was performed with Student’s t-test, using GraphPad Prism
4.0 (GraphPad Software Inc., La Jolla, CA, U.S.A.). The level
of statistical significance was set at P < 0Æ05.
Results
General medical history
There was no significant difference in general medical history
(e.g. cardiac diseases, diabetes) between the two groups,
except for high blood pressure that was more prevalent in PG
(16 ⁄93; 17%) than in CG (1 ⁄174; 0Æ5%) (P < 0Æ0001). No
PG patients were affected by atopy vs. 15 ⁄174 (8Æ6%) subjects
in CG (P < 0Æ01).
Dermatological medical history
In relation to medical history of skin cancer, the prevalence of
both basal cell carcinoma (BCC) and actinic keratosis (AK)
was 1% (1 ⁄93) in PG. Nobody in PG had ever had squamous
cell carcinoma (SCC) or melanoma. In CG, the prevalence of
BCC was 3Æ4% (6 ⁄174), whereas the prevalence of AK, SCC
and melanoma was, for each, 0Æ6% (1 ⁄174). There was no
difference between the two groups in the familial dermato-
logical medical history of nonmelanoma skin cancer but there
was a significant difference in familial history of melanoma
between the two groups: CG 8% (14 ⁄174) vs. nobody in PG
(P < 0Æ05). As expected, a statistically significant difference
was registered in the familial history of psoriasis in PG in
comparison with CG (P < 0Æ01).
Phenotype ⁄clinical characteristics
The phototype was distributed as follows: phototype I: 1 ⁄93
(1%) in PG vs. 5 ⁄174 (3%) in CG; phototype II: 12 ⁄93
(13%) in PG vs. 61 ⁄174 (35%) in CG; phototype III: 63 ⁄93
(68%) in PG vs. 95 ⁄174 (55%) in CG; phototype IV: 17 ⁄93
(18%) in PG vs. 13 ⁄174 (7%) in CG. A lower number of
facial freckles was registered in PG (32 ⁄93, 34%) than in CG
(82 ⁄174, 47%) (P < 0Æ01).
Naevi count for each area and regional distribution
Psoriasis group subjects had a lower number of areas with
naevi in comparison with CG. The most striking result was for
0 naevi: 20 ⁄93 (22%) PG patients vs. 2 ⁄174 (1Æ1%) of CG
subjects (P < 0Æ0001). Figure 1 summarizes the number of
areas with naevi in PG and CG subjects. We have analysed the
range of naevi for every area; PG patients showed a lower
range in comparison with CG for all body areas (Fig. 2).
Regarding the < 10 naevi range: in PG 11 ⁄16 areas were
involved vs. all areas in CG. There was a statistically significant
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Psoriasis and melanocytic naevi, N. Balato et al. 1265
Fig 1. The number of areas with naevi in psoriasis group (PG) and
control group (CG) subjects. On the x-axis numbers from 0 to 16
indicate the total number of involved areas (e.g. 1 = one area
involved by naevi; 16 = 16 areas involved by naevi).
difference in all areas except for G and I (P < 0Æ0001). For
the 11–30 naevi range: in PG 9 ⁄16 areas were involved vs.
14 ⁄16 areas in CG. A statistically significance was recorded in
7 ⁄16 areas (P < 0Æ001). For the 31–50 and > 50 naevi
ranges: no areas were reported in PG compared with 8 ⁄16 in
CG for the 31–50 range and just 1 ⁄16 for the > 50 range. No
statistically significant difference was detected.
Ten of 93 (11%) patients in PG had at least one lesion clini-
cally diagnosed as a congenital naevus vs. 28 ⁄174 (16%) in CG
(P < 0Æ01); in Table 3 dermoscopic features of congenital mel-
anocytic naevi are summarized. No statistically significant
difference was detected between the two groups in the distribu-
tion of dermoscopic patterns in the 16 body areas. A reticular
pattern was prevalent in areas A, B, F and H; a globular pattern
was dominant in areas C, D, G, K, M, N, O and P; a reticulo-
globular pattern was present in areas A, C, D, L, M and N; and a
pattern of diffuse brown pigment with dots was localized in
areas J, M and K. Our distribution data fit with the study of
Changchien et al.25 The prevalence of atypical naevi was lower
in PG than in CG, respectively 3 ⁄93 (3%) vs. 20 ⁄174 (11Æ5%)
(P < 0Æ01).
Gene expression in peripheral blood mononuclear cells
To test the hypothesis that IL-1a, IL-6 and TNF-a may inhi-
bit melanogenesis and melanocytic growth we sought to
analyse their gene expression at the PBMC level in PG and
CG. Fourteen subjects from each group were selected based
on naevi range: the first subgroup included seven subjects
from PG and seven from CG with 11–30 naevi range; the
second subgroup was constituted by seven subjects from PG
with 11–30 naevi range and seven from CG with < 10
naevi range. Comparing IL-1a, IL-6 and TNF-a levels in
subjects within the first subgroup, we found that all these
cytokines were higher in patients with psoriasis (Fig. 3, left
column) (P < 0Æ01). No statistically significant difference
was detected in gene expression of IL-1a, IL-6 and TNF-a
within the second subgroup between CG and PG (Fig. 3,
right column).
1266 Psoriasis and melanocytic naevi, N. Balato et al.

(a)

(b)

Fig 2. Charts showing the 16 body areas analysed. Naevi ranges are indicated by coloured boxes. CG, control group; PG, psoriasis group.

matched controls. We found significantly fewer naevi in PG

Discussion compared with CG: 22% of patients with psoriasis had no
This study describes the frequency and distribution of naevi melanocytic naevi vs. 1Æ1% in CG. This finding has not
in 93 adult patients with psoriasis and 174 adult aged- previously been reported in patients with psoriasis. A similar

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 Psoriasis and melanocytic naevi, N. Balato et al. 1267

Table 3 Predominant dermoscopic pattern of congenital naevi in involved in psoriasis pathogenesis have a role in melanogene-
psoriasis group and control group sis (Table 1). In particular, IL-1a, IL-6, TNF-a and TGF-b1
may inhibit melanogenesis and melanocytic growth because of
Dermoscopic Psoriasis Control their inhibitory effects on tyrosinase activity; the same cyto-
pattern group, n (%) group, n (%) kines are involved in the upregulation of keratinocyte prolifer-
Reticular 1 (3) 9 (24) ation in the pathogenesis of psoriasis.7–10 Swope et al.
Globular 4 (11) 7 (18) investigated the possibility that IL-1a, IL-6 and TNF-a could
Reticuloglobular 2 (5) 5 (13) have regulatory activity on melanization and proliferation of
Diffuse brown 3 (8) 5 (13)
cultured normal human melanocytes. All three cytokines elic-
pigment with dots
Other (e.g. presence 0 2 (5) ited a cytostatic, not cytotoxic, dose-dependent decreasing
of hair) effect in the tyrosinase activity (IL-1a >> TNF-a >> IL-6).11
These represented the basis by which we hypothesized that
Percentages are calculated on the total number (38) of congenital psoriatic subjects could have a lower number of naevi. Our
melanocytic naevi of both groups. findings that IL-1a, IL-6 and TNF-a gene expression is higher
in patients with psoriasis having the same naevi range as
healthy controls may support this immunological link between
inflammation and melanogenesis in psoriasis. Further, the
absence of disparity in the abovementioned cytokine levels
among PG with 11–30 naevi range vs. CG with < 10 naevi
range could reinforce this hypothesis.
The report that TNF-a blocking may influence the immuno-
logical and inflammatory mechanisms of vitiligo, favouring
melanization, also sustains this theory.31–33 Bovenschen et al.21
described outbreaks of eruptive benign melanocytic naevi dur-
ing immunosuppressive therapy (including anti-TNF-a treat-
ment for psoriasis). The most plausible theory that may
account for the formation of eruptive naevi postulates that an
intact immunological state normally inhibits the proliferation
of melanocytic lesions.19,20 Immune suppression, or even a
change in T cells, might induce MSH or melanoma growth
stimulatory activity (MGSA), which are endogenous growth
factors for normal melanocytes. Deregulation of the MGSA
gene might lead to higher expression of the MGSA protein,
which in turn might stimulate growth and development of
melanocytes.19–22
In our study, we found that in PG 11% of patients had at
least one lesion clinically diagnosed as a congenital naevus vs.
16% in CG and we found that the prevalence of atypical naevi
Fig 3. The mean values of the control group (CG) were set as 100% was lower in PG (3%) than in CG (11Æ5%). Moreover, nobody
and tumour necrosis factor (TNF)-a, interleukin (IL)-1a and IL-6 in PG had ever had melanoma, whereas the prevalence of mel-
levels in the psoriasis group (PG) are presented as a percentage of
anoma was 0Æ6% in CG; we also report a statistically signifi-
those in the CG. The first subgroup (11–30 naevi range) is
cant difference in melanoma medical history between the two
represented in the left column, whereas the second subgroup (PG
with 11–30 naevi range and CG with < 10 naevi range) in the right
groups: nobody in PG vs. 8% in CG (P < 0Æ05). These data
column. Each of the four study groups contained seven subjects. NS, could be also supported by the findings of Ahmed et al.34 who
not significant. hypothesized that IL-1a, IL-6 and TNF-a may protect
common naevi from malignant transformation.
association has already been established between atopic No PG patients were affected by atopy vs. 8Æ6% of patients
dermatitis and development of naevi. It is reported that chil- in CG. There has been considerable interest in defining the re-
dren with atopic dermatitis have few melanocytic naevi and lationship between the expression of allergic and Th1-medi-
a low melanoma risk.27–30 Broberg and Augustsson27 specu- ated diseases. Rabin and Levinson presented a model whereby
lated that the low number of naevi in patients with atopic active Th1 inflammation may suppress the development of
dermatitis was probably due to immunological mechanisms atopy, and atopy may suppress the severity but not necessarily
involved, hypothesizing the possible role of inflammatory the onset of autoimmunity. Drugs may also induce similar
cytokines. immunological effects, as the development of atopic dermatitis
Immunological interactions between psoriasis and melano- has been reported following anti-TNF therapy for rheumatoid
genesis may be present because some of the cytokines arthritis.35

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BJD  2011 British Association of Dermatologists 2011 164, pp1262–1270
1268 Psoriasis and melanocytic naevi, N. Balato et al.
In relation to medical history of skin cancer, the prevalence
of AK was similar in PG and CG, whereas the prevalence of
BCC was lower in PG than CG (1% and 3Æ4%, respectively).
Nobody in PG had ever had SCC, whereas the prevalence of
SCC was 0Æ6% in CG. Recent studies have shown that psoriatic
patients with BCC have evidence of increased DNA damage and
defective DNA repair compared with those psoriatic subjects
without BCC.36–38 Interestingly, Dybdahl et al.38 reported that
psoriatic patients without BCC had marginally higher repair
than controls, suggesting that skin cancers may occur in a sub-
group of patients with psoriasis, while others may be pro-
tected. It is conceivable that in some patients with psoriasis,
hyperproliferation of keratinocytes may protect against the
effects of sun damage when DNA repair mechanisms are intact.
Indeed, the occurrence of SCC in psoriatic subjects is exceed-
ingly rare39 in patients who have never received PUVA therapy.
In conclusion, we can assert that, at least in our sample,
psoriatic subjects showed a smaller number of melanocytic
naevi, including atypical ones; we hypothesize that the pro-
inflammatory cytokine network in psoriasis skin might inhibit
melanogenesis, melanocyte growth and ⁄or progression to
naevi. As far as we know, this is the first preliminary study of
the relationship between psoriasis and melanocytic naevi. On
the basis of these observations, it will be important to investi-
gate further the possible immunological link between psoriasis
and melanogenesis especially from an immunohistochemical
point of view.
What’s already known about this topic?
• It has been reported that patients with atopic dermatitis
have fewer melanocytic naevi and a lower melanoma
risk than controls.
• It is not known whether this is also the case in patients
with psoriasis.
What does this study add?
• Our results show that psoriatic subjects present fewer
naevi than controls. This finding may open a new out-
look on the connections between psoriasis and other
conditions related to melanogenesis.
Acknowledgments
The authors kindly thank Gabriella Fabbrocini, MD for statis-
tical analysis.
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 Psoriasis and melanocytic naevi, N. Balato et al. 1269

26 Johr RH. Dermoscopy: alternative melanocytic algorithms – the Others __ __ __ __ __ __ __ __ __ __

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20:143–8.
__ __ __ __ __ __ __ __ __ __
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of melanoma in patients with atopic dermatitis. J Eur Acad Dermatol
Venereol 2008; 22:1423–8. Dermatological medical history
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and malignant melanoma. Am J Dermatopathol 1995; 17:222–9. If yes, how long have you had the condition?
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Psoriasis treatment ongoing:
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Familial dermatological medical history

Appendix 1. Questionnaire: naevi count and Is there a history of skin cancer in your family?
psoriasis BCC or SCC cancer?
yes h no h
Personal data If yes, could you please specify
Mother yes h no h
First initial __ First letter of surname __ Sex: M h F h Father yes h no h
Age:__ __ Brothers or sisters yes h no h
Melanoma cancer?
Personal medical history yes h no h
If yes, could you please specify
Have you ever had at least one of these medical problems? Mother yes h no h
Heart diseases yes h no h Father yes h no h
High blood pressure yes h no h Brothers or sisters yes h no h
Type II diabetes mellitus yes h no h Does ⁄did anyone in your family have psoriasis?
Hypercholesterolaemia yes h no h yes h no h
Hypertriglyceridaemia yes h no h If yes, could you please specify
Liver diseases yes h no h Mother yes h no h
Kidney diseases yes h no h

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BJD  2011 British Association of Dermatologists 2011 164, pp1262–1270
1270 Psoriasis and melanocytic naevi, N. Balato et al.

Father yes h no h
Brothers or sisters yes h no h

Skin examination
Fitzpatrick skin type
I h II h III h IV h V h
Presence of face freckles
yes h no h
Naevi counts (> 2 mm)
Areas
A ()0 ()<10 ()11-30 ()31-50 ()>50
B ()0 ()<10 ()11-30 ()31-50 ()>50
C ()0 ()<10 ()11-30 ()31-50 ()>50
D ()0 ()<10 ()11-30 ()31-50 ()>50
E ()0 ()<10 ()11-30 ()31-50 ()>50
F ()0 ()<10 ()11-30 ()31-50 ()>50
G ()0 ()<10 ()11-30 ()31-50 ()>50
H ()0 ()<10 ()11-30 ()31-50 ()>50
I ()0 ()<10 ()11-30 ()31-50 ()>50
J ()0 ()<10 ()11-30 ()31-50 ()>50
K ()0 ()<10 ()11-30 ()31-50 ()>50
L ()0 ()<10 ()11-30 ()31-50 ()>50
M ()0 ()<10 ()11-30 ()31-50 ()>50
N ()0 ()<10 ()11-30 ()31-50 ()>50
O ()0 ()<10 ()11-30 ()31-50 ()>50 Atypical vascular pattern yes h no h
P ()0 ()<10 ()11-30 ()31-50 ()>50 Irregular streaks yes h no h
Presence of congenital naevi Irregular dots ⁄globules yes h no h
yes h no h Irregular pigmentation yes h no h
Presence of atypical naevi Regression structures yes h no h
yes h no h Please, specify the area
Dermoscopic examination __ __ __ __ __ __ __ __ __ __
Atypical pigment network yes h no h Schematic figure illustrating the 16 areas (A–P) studied.
Blue-whitish veil yes h no h From ref. 28.

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BJD  2011 British Association of Dermatologists 2011 164, pp1262–1270