AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Background

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

Dereure² noted that Naegeli-Franceschetti-Jadassohn syndrome (NFJS) and DPR are 2 allelic ectodermal dysplasias related to mutations of dominant gene coding for keratin 14.

Pathophysiology

NFJS and DPR may be variations on the same genetic defect. The 2 syndromes are both allelic, both caused by dominant mutations in KRT14.

NFJS and DPR are ectodermal dysplasias. They are inherited in an autosomal dominant fashion.³ Both manifest with the absence of dermatoglyphics, reticulate hyper pigmentation 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.

Still, the relationship of NFJS must be further clarified. 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.⁴

Sprecher et al⁵ assessed linkage for chromosome 17q in a large Swiss family with NFJS. Band 17q has been postulated to contain the gene for NFJS.⁶ Sprecher et al⁵ 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, Sprecher et al⁵ 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.⁶

Frequency

United States

This condition is rare. Approximately 4 cases of DPR have been reported in the United States.

International

Since first described in 1958, approximately 12 cases have been reported. Most of the cases were reported in Europe, with rare reports in America and Asia. Brar et al⁷ noted it in a 12-year-old Indian patient.

Mortality/Morbidity

No morbidity and mortality rates of DPR have been reported.

Race

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

Sex

No sex predilection is documented.

Age

The reticulate pigmentation occurs at birth or during early childhood.

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

History

The primary clinical feature of 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.

Physical

Most reported cases have demonstrated a clinical triad of reticulate hyperpigmentation, mild nonscarring alopecia, and mild onychodystrophy. 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

Causes

DPR is believed to be a genetic disorder with probable autosomal dominant inheritance.³

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

The diagnosis of DPR is based on the presence of the clinical triad and a typical histopathologic picture; however, the following hyperpigmentation disorders should be considered and excluded:

• Acromelanosis progressiva
• Hereditary symmetric dyschromatosis of Dohi
• Reticular acropigmentation of Kitamura
• Heterochromia extremitarium
• Reticulate pigmented dermatosis of the flexures
• Congenital diffuse mottling of the skin
• Hereditary universal dyschromatosis
• Dyskeratosis congenita syndrome
• Franceschetti-Jadassohn or Naegeli syndrome

Points of differentiation

Each of the following demonstrate a distinctive distribution of pigmentation with diffuse frecklelike or reticulate hyperpigmentation on the dorsa of the hands and feet, the extremities, or the flexural areas (axillae, groin): acromelanosis progressiva, hereditary symmetric dyschromatosis of Dohi, reticular acropigmentation of Kitamura, heterochromia extremitarium, and reticulate pigmented dermatosis of the flexures.

Differentiation from congenital diffuse mottling of the skin can be made histopathologically by demonstrating clubbing of the rete ridges and hyperpigmentation of the basal layer without pigmentary incontinence.

Hereditary universal dyschromatosis is associated with hyperpigmented and hypopigmented macules of irregular shape and size, as well as small stature and high-tone deafness.

Dyskeratosis congenita syndrome is an X-linked condition and occurs most commonly in males, usually, in males older than 5 years. In addition to reticulate hyperpigmentation, nail dystrophy, and hyperkeratosis and atrophy of the palms and soles, patients with dyskeratosis congenita also have leukokeratosis of mucosal surfaces and blood dyscrasias.

Franceschetti-Jadassohn (Naegeli) syndrome is an autosomal dominant condition with gray-brown reticulate pigmentation of the trunk and neck that fades after adolescence. Dental anomalies and a bleeding tendency are frequently observed in these patients.

Franceschetti-Jadassohn (Naegeli) syndrome and DPR share complete absence of dermatoglyphics; a reticulate pattern of hyperpigmentation; palmoplantar keratoderma; abnormal sweating; and anomalies of the teeth, hair, and skin.⁸

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Lab Studies

No abnormal laboratory findings have been consistently documented.

Procedures

Cutaneous biopsy findings may be helpful when making the diagnosis. Excisional or punch biopsy of the reticular pigmentation may be helpful.

Histologic Findings

The typical histopathologic picture shows liquefaction degeneration of the basal layer and dermal pigmentary incontinence. That is, an interface dermatitis can be present.

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Medical Care

No specific treatment exists for this disorder, except for symptomatic management of some of the associated conditions, such as palmoplantar hyperkeratosis. For hyperkeratosis, topical retinoic acids and keratolytics may be beneficial. Nonscarring blisters are generally transient and self-healing. Cold compress may suffice.

Activity

Advise patients to avoid sun exposure, which may trigger blister formation.

FOLLOW-UP

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Deterrence/Prevention

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

Complications

No serious complications are known. Some conditions mentioned in the literature are probably coincidental rather than complications.

Prognosis

The hyperpigmentation persists throughout life, showing no tendency of spontaneous fading.

MISCELLANEOUS

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

This is a rare syndrome and may not be readily recognized.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

1. Bu TS, Kim YK, Whang KU. A case of dermatopathia pigmentosa reticularis. J Dermatol. Apr 1997;24(4):266-9. [Medline].
2. Dereure O. [Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis. Two allelic ectodermal dysplasias related to mutations of dominant gene coding for keratin 14]. Ann Dermatol Venereol. Jun-Jul 2007;134(6-7):595. [Medline].
3. Heimer WL 2nd, Brauner G, James WD. Dermatopathia pigmentosa reticularis: a report of a family demonstrating autosomal dominant inheritance. J Am Acad Dermatol. Feb 1992;26(2 Pt 2):298-301. [Medline].
4. Itin PH, Lautenschlager S, Meyer R, Mevorah B, Rufli T. Natural history of the Naegeli-Franceschetti-Jadassohn syndrome and further delineation of its clinical manifestations. J Am Acad Dermatol. Jun 1993;28(6):942-50. [Medline].
5. Sprecher E, Itin P, Whittock NV, McGrath JA, Meyer R, DiGiovanna JJ, et al. Refined mapping of Naegeli-Franceschetti- Jadassohn syndrome to a 6 cM interval on chromosome 17q11.2-q21 and investigation of candidate genes. J Invest Dermatol. Sep 2002;119(3):692-8. [Medline].
6. Whittock NV, Coleman CM, McLean WH, Ashton GH, Acland KM, Eady RA, et al. The gene for Naegeli-Franceschetti-Jadassohn syndrome maps to 17q21. J Invest Dermatol. Oct 2000;115(4):694-8. [Medline].
7. Brar BK, Mehta V, Kubba A. Dermatopathia pigmentosa reticularis. Pediatr Dermatol. Sep-Oct 2007;24(5):566-70. [Medline].
8. Lugassy J, Itin P, Ishida-Yamamoto A, Holland K, Huson S, Geiger D, et al. Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis: two allelic ectodermal dysplasias caused by dominant mutations in KRT14. Am J Hum Genet. Oct 2006;79(4):724-30. [Medline].
9. Fulk CS. Primary disorders of hyperpigmentation. J Am Acad Dermatol. Jan 1984;10(1):1-16. [Medline].
10. Maso MJ, Schwartz RA, Lambert WC. Dermatopathia pigmentosa reticularis. Arch Dermatol. Jul 1990;126(7):935-9. [Medline].
11. Rycroft RJ, Calnan CD, Allenby CF. Dermatopathia pigmentosa reticularis. Clin Exp Dermatol. Mar 1977;2(1):39-44. [Medline].
12. Schnur RE, Heymann WR. Reticulate hyperpigmentation. Semin Cutan Med Surg. Mar 1997;16(1):72-80. [Medline].
13. van der Lugt L. Dermatopathia pigmentosa reticularis hyperkeratotica et mutilans. Dermatologica. 1970;140(5):294-302. [Medline].

Article Last Updated: Feb 1, 2008