**3. Histopathology of nail psoriasis**

Whereas the main criteria for psoriasis of the skin also apply for ungual psoriasis there are some differences and, above all, there are signs not seen in the rest of the skin.

Pits are the most frequent lesions in nail psoriasis (Figs. 3, 4) with roughly 70% of the patients presenting at least some of these characteristic tiny depressions (Zaias, 1969, Tham et al, 1988). Histologically, their appearance varies slightly. In the distal nail plate, they are seen as a depression in the nail plate surface that may be lined by some parakeratotic nail cells. The more proximal the biopsy is taken, the more parakeratosis is left. Under the proximal nail fold there are not yet pits but saucer-shaped small areas of parakeratosis. When these do not break out as it most commonly happens tiny white spots remain visible giving rise to spotted nails. Usually the rest of the nail organ appears normal and only in rare circumstances is a tiny inflammatory psoriatic lesion seen at the proximal tip of the matrix. Whether or not the pits may also originate from the most proximal portion of the ventral surface of the proximal nail fold (Zaias, 1990) remains a matter of dispute. Anyhow, it is surprising how rarely the original inflammatory matrix lesions giving rise to spots and pits are seen in histopathological slides.

Nail bed changes are the second most common ungual sign of psoriasis. They may present as salmon or oil spots, which represent a small psoriatic plaque of the nailbed entirely covered by the nail plate, as onycholysis when the psoriatic plaque extends to the hyponychium, or as subungual hyperkeratosis representing a hyperkeratotic psoriatic plaque. A typical salmon spot shows slight acanthosis of the nail bed epithelium, an inflammatory infiltrate mainly made up of lymphocytes that tend to migrate into the epithelium and cause spongiosis, as well as parakeratosis on top of the epithelium, which

Nail Psoriasis 147

however, in contrast to fungal elements they are homogeneously positive and have no

At the hyponychium, the normal granular layer is lost and the tight connection of the nail plate with the most distal portion of the nail bed is loosened. Parakeratosis develops

Both the matrix and nail bed may transform to an epidermis-like pattern of differentiation in

Isolated involvement of the middle matrix appears to be less frequent. It leads to nail plate changes clinically often seen as psoriatic leukonychia. Histopathologically, the matrix shows acanthosis and spongiosis, a dense subepithelial inflammatory infiltrate mainly of lymphocytes that also migrate into the matrix epithelium. Neutrophils may be present and sometimes concentrate under the nail plate to form spongiform pustule-like collections. There may also be parakeratotic layers in the nail plate; these "paronychotic" cell layers are distinct from areas of incomplete nuclear disintegration, which are not infrequently seen in avulsed nail strips of ingrown nails. These inclusions of parakeratosis in the nail plate give

Fig. 5. Psoriatic leukonychia is seen when there is a psoriatic lesion in the middle or distal

Splinter haemorrhages are a characteristic of nail psoriasis not seen in onychomycosis. They are analogous to Auspitz' phenomenon of the skin. When the fragile thinned suprapapillary epithelial plate of a psoriasis lesion is traumatized a minute droplet of blood is seen to appear in a skin lesion because the epidermis has rete pegs and finger like dermal papillae. In contrast, the nail bed is unique to have rete ridges in parallel arrangement; when a microbleeding develops it forms a narrow stripe of haemorrhage, about 0.5 – 1mm wide and 3 – maximally 10 mm long (Fig. 8, 9). They are soon included by newly produced nail bed keratin and seen as small blood lakes between the papillomatous appearing keratosis of the

old lesions with development of a granular layer and some orthokeratosis.

membrane staining like fungi.

matrix

without attachment with the nail plate.

rise to the clinical picture of leukonychia (Fig. 5, 6, 7).

nail bed and the undersurface of the nail plate.

Fig. 3. Formation of psoriatic pits from a tiny inflammatory focus at the most proximal matrix.

Fig. 4. Histological picture of an incipient pit, which is seen as a saucer-shaped mass of parakeratosis on the matrix epithelium.

often contains neutrophils. In more pronounced acute lesions, Munro's microabscesses may be seen. Typical for psoriasis is the arrangement of parakeratosis in obliquely ascending columns. This and the lack of fungal elements in PAS stained slides helps to distinguish this pattern from onychomycosis, which also often exhibits neutrophil collections as seen in Munro's microabscesses. Psoriatic onycholysis is located more distally in the nail bed, but principally very similar to oil spots. The neutrophil exocytosis may be less pronounced, and in old lesions it may be difficult to make the diagnosis of nail psoriasis at all as the nailbed may develop a granular layer and layered orthokeratotic hyperkeratosis. Subungual hyperkeratosis in psoriasis may sometimes be extreme mimicking even pachyonychia congenita. Huge thickening of the keratosis with parakeratosis both in horizontal layers and oblique columns may be present along with serum inclusions. The latter may form large round to oval globules, but also present as very small longitudinal structures. These serum inclusions are PAS positive and may be difficult to be dífferentiated by the non-experienced;

Fig. 3. Formation of psoriatic pits from a tiny inflammatory focus at the most proximal

Fig. 4. Histological picture of an incipient pit, which is seen as a saucer-shaped mass of

often contains neutrophils. In more pronounced acute lesions, Munro's microabscesses may be seen. Typical for psoriasis is the arrangement of parakeratosis in obliquely ascending columns. This and the lack of fungal elements in PAS stained slides helps to distinguish this pattern from onychomycosis, which also often exhibits neutrophil collections as seen in Munro's microabscesses. Psoriatic onycholysis is located more distally in the nail bed, but principally very similar to oil spots. The neutrophil exocytosis may be less pronounced, and in old lesions it may be difficult to make the diagnosis of nail psoriasis at all as the nailbed may develop a granular layer and layered orthokeratotic hyperkeratosis. Subungual hyperkeratosis in psoriasis may sometimes be extreme mimicking even pachyonychia congenita. Huge thickening of the keratosis with parakeratosis both in horizontal layers and oblique columns may be present along with serum inclusions. The latter may form large round to oval globules, but also present as very small longitudinal structures. These serum inclusions are PAS positive and may be difficult to be dífferentiated by the non-experienced;

parakeratosis on the matrix epithelium.

matrix.

however, in contrast to fungal elements they are homogeneously positive and have no membrane staining like fungi.

At the hyponychium, the normal granular layer is lost and the tight connection of the nail plate with the most distal portion of the nail bed is loosened. Parakeratosis develops without attachment with the nail plate.

Both the matrix and nail bed may transform to an epidermis-like pattern of differentiation in old lesions with development of a granular layer and some orthokeratosis.

Isolated involvement of the middle matrix appears to be less frequent. It leads to nail plate changes clinically often seen as psoriatic leukonychia. Histopathologically, the matrix shows acanthosis and spongiosis, a dense subepithelial inflammatory infiltrate mainly of lymphocytes that also migrate into the matrix epithelium. Neutrophils may be present and sometimes concentrate under the nail plate to form spongiform pustule-like collections. There may also be parakeratotic layers in the nail plate; these "paronychotic" cell layers are distinct from areas of incomplete nuclear disintegration, which are not infrequently seen in avulsed nail strips of ingrown nails. These inclusions of parakeratosis in the nail plate give rise to the clinical picture of leukonychia (Fig. 5, 6, 7).

Fig. 5. Psoriatic leukonychia is seen when there is a psoriatic lesion in the middle or distal matrix

Splinter haemorrhages are a characteristic of nail psoriasis not seen in onychomycosis. They are analogous to Auspitz' phenomenon of the skin. When the fragile thinned suprapapillary epithelial plate of a psoriasis lesion is traumatized a minute droplet of blood is seen to appear in a skin lesion because the epidermis has rete pegs and finger like dermal papillae. In contrast, the nail bed is unique to have rete ridges in parallel arrangement; when a microbleeding develops it forms a narrow stripe of haemorrhage, about 0.5 – 1mm wide and 3 – maximally 10 mm long (Fig. 8, 9). They are soon included by newly produced nail bed keratin and seen as small blood lakes between the papillomatous appearing keratosis of the nail bed and the undersurface of the nail plate.

Nail Psoriasis 149

In pustular psoriasis, spongiform pustule formation is usually seen with collection of neutrophils gradually increasing in density toward the superficial layers of both the matrix

Fig. 8. Splinter haemorrhages develop when there is haemorrhage in the papillary rete

Fig. 9. Longitudinal section of a nail bed biopsy showing oval lakes of blood as sign of

ridges or when the horizontally running capillaries thrombose.

and nail bed epithelium (Fig. 10).

splinter haemorrhages.

Fig. 6. Munro's microabscesses in the deep nail plate appear as leukonychic spots in the nail

Fig. 7. This nail plate is irregular in its structure and contains many Munro's microabscesses making it appear intransparent and grayish-white

Acrodermatitis continua suppurativa is a particular form of pustular psoriasis; however, histopathologically three forms exist: with characteristic spongiform pustules, with marked spongiosis and even spongiotic vesicles, and a mixed form with spongiform pustules and spongiosis.

Fig. 6. Munro's microabscesses in the deep nail plate appear as leukonychic spots in the nail

Fig. 7. This nail plate is irregular in its structure and contains many Munro's microabscesses

Acrodermatitis continua suppurativa is a particular form of pustular psoriasis; however, histopathologically three forms exist: with characteristic spongiform pustules, with marked spongiosis and even spongiotic vesicles, and a mixed form with spongiform

making it appear intransparent and grayish-white

pustules and spongiosis.

In pustular psoriasis, spongiform pustule formation is usually seen with collection of neutrophils gradually increasing in density toward the superficial layers of both the matrix and nail bed epithelium (Fig. 10).

Fig. 8. Splinter haemorrhages develop when there is haemorrhage in the papillary rete ridges or when the horizontally running capillaries thrombose.

Fig. 9. Longitudinal section of a nail bed biopsy showing oval lakes of blood as sign of splinter haemorrhages.

et al, 2011).

80%.

et al, 2011).

**5. Immunogenetics** 

reproduced in all studies.

(Chiam et al, 2011).

be similar in Indian children (Nanda et al, 1990).

Nail Psoriasis 151

In a Swiss cohort of 1222 psoriasis patients, 9.4% suffered from nail involvement (Ruprecht

Whereas there is a striking difference in the frequency of familiar cases between psoriasis in Caucasian children (83%) as compared to Asian children (13.4%) ) nail psoriasis is insignificantly more frequent in Singaporean (35.8%) than in Dutch children (22.2%). Pitting is the most common nail sign (Chiam et al, 2011). The frequency of nail psoriasis appears to

Nail psoriasis is more common in psoriatic arthritis, the prevalence is usually greater than

It appears that nail disease is relatively more frequent in males than in females (Wittkowski

Psoriasis is a multifactorial disorder with a strong genetic background. Environmental cofactors play an important role in its manifestation. Various psoriasis susceptibility (PSORS) factors have been identified, of which PSORS1 on chromosome 6p21 has been

Nail psoriasis has more frequently a positive family history as compared to psoriasis of the skin (52.7% vs. 43.8%), is more often associated with psoriatic arthritis (29.7% vs. 11.5%), is more often linked to early onset psoriasis (74.1% vs. 65.5%) and is fewer positive for the HLA allele Cw\*0602 (33% vs. 50.3%) (Armesto et al, 2011, Gudjonsson et al, 2006). It may also be speculated that the IL23R polymorphism that is a common susceptibility factor for psoriasis (Cargill et al, 2007) and is not or only rarely found in Han Chinese may account for the higher rate of familiarity of psoriasis in Caucasians as compared to Asians

Nail psoriasis is associated with a higher frequency of psoriatic arthritis and a more progressive form of the disease (Williamson et al, 2004, Serarslan et al, 2007). The skin and

Psoriasis patients with nail involvement have a longer disease duration, higher disease severity, more than double the frequency of psoriatic arthritis, more pronounced impairment of disease related quality of life, they were statistically significantly longer off

Nail psoriasis is characterized by pits, salmon spots, onycholysis, subungual hyperkeratosis and some more signs that are less frequent. The psoriatic nail changes may be classified according to their origin: Pitting, leukonychia, nail plate thickening, crumbling and red spots in the lunula originate in the matrix whereas oil drop discoloration (salmon spots), nail bed hyperkeratosis, onycholysis and splinter haemorrhages derive from the nail bed. Swelling of the proximal nail fold reflects paronychia and swelling of the distal interphalangeal joint is suggestive of psoriatic arthritis. Psoriatic pachydermoperiostosis

work, and had a 2.5 fold higher rate of in-hospital treatments (Augustin et al, 2010).

nail lesion usually manifest before the arthritis (Mease , 2002).

**6. Clinical lesions of nail psoriasis** 

leads to enlargement of the entire distal phalanx.

Fig. 10. Acrodermatitis continua suppurativa of Hallopeau with massive spongiform pustule formation; a. Huge amounts of neutrophils are seen in the nail bed epithelium, b. Collections of neutrophils are embedded in a matrix of cornified nail bed keratinocytes.

#### **4. Frequency**

Psoriasis prevalence is about 2% in Central Europe and 1-3% worldwide. At any given time point, about 10 – 50% of the psoriatics present nail changes (Scher, 1985, Augustin et al, 2010), but approximately 90% of all psoriatic subjects will have developed nail alterations during life time. The prevalence of nail psoriasis in men is about 11% higher than in women (Augustin et al, 2010). Isolated nail psoriasis is seen in 1 – 5% (Lavaroni et al, 1994).

a)

b)

Psoriasis prevalence is about 2% in Central Europe and 1-3% worldwide. At any given time point, about 10 – 50% of the psoriatics present nail changes (Scher, 1985, Augustin et al, 2010), but approximately 90% of all psoriatic subjects will have developed nail alterations during life time. The prevalence of nail psoriasis in men is about 11% higher than in women

Fig. 10. Acrodermatitis continua suppurativa of Hallopeau with massive spongiform pustule formation; a. Huge amounts of neutrophils are seen in the nail bed epithelium, b. Collections of neutrophils are embedded in a matrix of cornified nail bed keratinocytes.

(Augustin et al, 2010). Isolated nail psoriasis is seen in 1 – 5% (Lavaroni et al, 1994).

**4. Frequency** 

In a Swiss cohort of 1222 psoriasis patients, 9.4% suffered from nail involvement (Ruprecht et al, 2011).

Whereas there is a striking difference in the frequency of familiar cases between psoriasis in Caucasian children (83%) as compared to Asian children (13.4%) ) nail psoriasis is insignificantly more frequent in Singaporean (35.8%) than in Dutch children (22.2%). Pitting is the most common nail sign (Chiam et al, 2011). The frequency of nail psoriasis appears to be similar in Indian children (Nanda et al, 1990).

Nail psoriasis is more common in psoriatic arthritis, the prevalence is usually greater than 80%.

It appears that nail disease is relatively more frequent in males than in females (Wittkowski et al, 2011).
