Dermatopathia Pigmentosa Reticularis

Updated: Jun 22, 2023
  • Author: Melba Estrella, MD; Chief Editor: Dirk M Elston, MD  more...
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Overview

Practice Essentials

Dermatopathia pigmentosa reticularis (DPR) is a very rare disorder with the diagnostic triad of generalized reticulate hyperpigmentation, noncicatricial alopecia, and onychodystrophy. Many other dermatologic findings have been associated with this triad. These findings include adermatoglyphia, hypohidrosis or hyperhidrosis, palmoplantar hyperkeratosis, and acral dorsal nonscarring blisters. [1, 2]  The reticulate pigmentation of DPR occurs at birth or during early childhood.

Signs and symptoms

The primary clinical feature of dermatopathia pigmentosa reticularis (DPR) is the occurrence of reticulate hyperpigmented macules at birth or in early childhood, usually by age 2 years.

The hyperpigmentation persists throughout life, showing no tendency of spontaneous fading. The reticulate network of hyperpigmented macules occurs particularly on the trunk, neck, and proximal areas of the limbs.

Most reported cases of DPR have demonstrated a clinical triad of reticulate hyperpigmentation, mild nonscarring alopecia, and mild onychodystrophy. Al-Hamdi et al [3]  reported a case of DPR with late onset of both alopecia and onychodystrophy, proposing that the reticulate hyperpigmentation may be the only feature present before puberty. Other associated features may include the following:

  • Punctate or diffuse palmoplantar hyperkeratosis

  • Darkly pigmented nipples

  • Nonscarring blisters on the dorsa of hands and feet following minor trauma or sun exposure

  • Hyperhidrosis or hypohidrosis

  • Adermatoglyphia (loss of dermal ridges on fingers and toes)

  • Thin eyebrows and sparse pubic and axillary hair

It is possible that Naegeli-Franceschetti-Jadassohn syndrome (NFJS), poikiloderma Clericuzio type, and dyskeratosis congenita can overlap, with a presentation of prenatal and postnatal growth restriction, developmental delay, microcephaly, and pigmentation pathology. [4]

No serious complications are known for DPR. A few cases of DPR showing extracutaneous manifestations have been addressed in the literature as probable coincidences rather than complications.

Early-onset gastric carcinoma in a male with DPR was noted by Tunca et al in 2008. [5]  Goh et al [6]  reported a case of DPR caused by a recurrent KRT14 mutation in which the patient had digital fibromatosis and wiry scalp hair. [6]

Very few cases of DPR have been described to present with corneal opacity and superficial punctate spots, but only one case has been reported presenting bilateral Salzmann nodular degeneration of the cornea. [2, 7]

Diagnostics

Dermatopathia pigmentosa reticularis (DPR) does not warrant laboratory studies beyond genetic testing because of the lack of consistent report of abnormal results. Al-Hamdi [3]  et al reported an isolated case of DPR with elevated serum cortisol and hepatomegaly.

Excisional or punch cutaneous biopsy of the reticular pigmentation may be helpful when making the diagnosis of DPR. The typical histopathologic picture of DPR shows hyperpigmentation of the basal layer with cytoplasmic vacuolization and the presence of melanophages within the reticular dermis. [2, 3]  That is, an interface dermatitis can be present.

Management

No specific treatment exists for dermatopathia pigmentosa reticularis (DPR). Symptomatic management of palmoplantar hyperkeratosis and other secondary changes can be addressed with topical steroids, keratolytics, and emollients. [8]  Nonscarring blisters are generally transient and self-healing. Cold compresses may suffice.

Advise patients with DPR to avoid sun exposure and minor trauma, which may trigger blister formation.

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Background

Dereure [9] noted that Naegeli-Franceschetti-Jadassohn syndrome (NFJS) and DPR are two allelic ectodermal dysplasias related to mutations of the dominant gene coding for keratin 14 (KRT14). Other diseases caused by defects in keratin 14 include epidermolysis bullosa and Dowling-Mera disease. [10, 11, 12] Severe keratin 5 and 14 mutations induce down-regulation of junction proteins in keratinocytes, [13] which likely underlies all of these diseases. A number of missense mutations in KRT14 causing a DPR/NFJS phenotype have been reported. [14, 15] DPR resembles NFJS; they share reticulate pigmentation through adulthood, dental abnormalities, and alopecia. DPR and NFJS are considered to be allelic disorders, attributable to mutations on the nonhelical (E1/V1) head domain in the KRT14 gene, with consequent premature termination of protein synthesis. [16, 8]

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Pathophysiology

Naegeli-Franceschetti-Jadassohn syndrome (NFJS) and dermatopathia pigmentosa reticularis (DPR) are ectodermal dysplasias inherited in an autosomal dominant fashion. [17] The two disorders are both allelic and caused by dominant mutations in KRT14. Missense mutations can cause either of these diseases. [15] Both can manifest with the absence of dermatoglyphics, reticulate hyperpigmentation of the skin, hypohidrosis, and heat intolerance. Palmoplantar keratoderma, nail dystrophy, and enamel defects are common in NFJS, whereas diffuse alopecia is only seen in DPR.

In some NFJS pedigrees, the reticulate pigmentation fades after puberty and may disappear completely in old age. Hypohidrosis, the main problem for the patients, remains constant. Teeth are always severely affected, leading to early total loss. All patients with NFJS lack dermatoglyphics. Diffuse palmoplantar keratoderma may coexist with punctate keratoses that are sometimes accentuated in the creases or exhibit a linear pattern. Congenital malalignment of the great toenails can occur. [18]

Burger et al [19] examined 9 members of a five-generation Swiss family with overlapping signs of NFJS and DPR. Sanger sequencing of genomic DNA derived from patient lymphocytes revealed a unique 2-bp insertion in exon 1 of KRT14, leading to a frameshift and premature stop codon. They postulate that the identification of this intrafamilial overlap of phenotypes with the same KRT14 frameshift variant challenges the idea that DPR and NFJS are distinct disorders, representing instead a continuous phenotypical spectrum. [19]

p53 can act as a co-repressor to regulate KRT14 expression while epidermal cell differentiation occurs. [20] A half-site occurring on the p53-binding site on the KRT14 promoter involves activation by p63, suggesting that the differing p53-binding site's lengths could determine the gene regulation by different members of the p53 family of proteins. [21]

In 2002 Sprecher et al [22] assessed linkage for 17q in a large Swiss family with NFJS. Band 17q has been postulated to contain the gene for NFJS. They found a considerably narrow NFJS gene region, from 27 cM to 6 cM, flanked by D17S933 and D17S934, with a maximum multipoint logarithm of the odds score of 2.7 at marker locus D17S800. In addition, they studied a small family with DPR and reported that the linkage data they assembled suggested that DPR may map to band 17q. On 17q, the NFJS critical interval spans approximately 5.4 Mb and contains a minimum of 45 distinct genes. [23]

Goh et al [6] noted a patient of Malay ancestry with DPR secondary to a recurrent KRT14 p.R125C mutation. The patient had wiry scalp hair and digital fibromatous thickening in addition to reticulate hyperpigmentation over his trunk and proximal limbs. He also had onychodystrophy without noncicatricial alopecia.

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Etiology

Dermatopathia pigmentosa reticularis (DPR) is believed to be a genetic disorder of autosomal dominant inheritance. [17]

Apoptosis may play a key role in its pathogenesis, as evidenced by increased apoptotic activity in the basal cell layer expressing keratin 14. [8]

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Epidemiology

Frequency

Since first described in 1958, dermatopathia pigmentosa reticularis (DPR) has been acknowledged as a very rare disorder, with approximately 21 reported cases among the regions of America, Europe, and Asia. [19]

Race-, sex-, and age-related information

Although most cases of DPR are reported in the European and US literature, no evidence indicates that DPR is associated with any particular race.

No sex predilection is documented for DPR.

The reticulate pigmentation associated with DPR occurs at birth or during early childhood.

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Prognosis

The hyperpigmentation associated with dermatopathia pigmentosa reticularis (DPR) persists throughout life, showing no tendency of spontaneous fading.

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Patient Education

Counsel the patient that the reticular hyperpigmentation persists throughout life, showing no tendency of spontaneous fading.

Consider genetic counseling to advise affected patients and their families of the medical implications of the disease and its pattern of inheritance. [7]

Advise patients with dermatopathia pigmentosa reticularis (DPR) to avoid sun exposure, which may trigger blister formation.

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