Approach to reticulate hyperpigmentation

Authors


  • Conflict of interest: none declared.

Dr Vasanop Vachiramon, Division of Dermatology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Rajthevi, Bangkok 10400, Thailand
E-mail: vasanop@gmail.com

Summary

Reticulate hyperpigmentation is a feature of a number of conditions, which differ in age of onset and distribution of the lesions. Associated clinical findings (e.g. hair, nail, teeth, systemic involvement), are used to differentiate between the conditions. Histopathological examination is useful in some disorders. Diagnosing the disorders is important, because the underlying causes may be treatable, and some of the disorders are associated with malignancies and life-threatening systemic involvement. In this review, I present a concise, systematic approach to the treatment of the patient with reticulate hyperpigmentation.

Introduction

Reticulate hyperpigmentation is characterized by net-like patterns of cutaneous hyperpigmentation, and is characteristic of a number of congenital and acquired conditions. The aim of this article is to categorize each condition based on the typical age of onset (infancy/childhood vs. adolescent/adult) (Table 1; Figs 1, 2), and by lesion distribution and associated clinical findings. Disorders occurring at birth or during early childhood usually have a genetic basis; however, some genetic disorders may first become apparent later in life. Detailed family and personal history, including any drug and chemical exposure, and complete dermatological and general physical examinations are essential diagnostic tools. Reticulate erythema (a feature of conditions such as cutis mamorata, livedo reticularis, reticulated erythematous mucinosis, erythema infectiosum) and poikiloderma (a mixture of hypopigmentation and hyperpigmentation, with telangiectasia and skin atrophy, found in conditions such as Rothmund–Thomson syndrome, poikiloderma of Civatte, and poikiloderma atrophicans vasculare) must be excluded from the diagnosis.

Table 1.   Differential diagnosis of reticulate hyperpigmentation, based on age of onset.
Typical onset
Infancy and childhood
 Dermatopathia pigmentosa reticularis
 Dyskeratosis congenita
 Epidermolysis bullosa simplex with mottled pigmentation
 Fanconi anaemia
 Incontinentia pigmenti (stage 3)
 Mitochondrial diseases
 Naegeli–Franceschetti–Jadassohn syndrome
 Revesz syndrome
 X-linked reticulate pigmentary disorders (affected males, carrier females)
Adolescence and adulthood
 Ashy dermatosis
 ‘Dirty neck’ in atopic dermatitis
 Confluent and reticulate papillomatosis of Gougerot and Carteaud
 Dowling–Degos disease
 Drug-induced reticulate pigmentation
 Erythema ab igne
 Galli–Galli disease
 Kitamura acropigmentation
 Lichen planus pigmentosus
 Pigmentatio reticularis facei et colli
 Pigmented contact dermatitis
 Postinflammatory hyperpigmentation
 Prurigo pigmentosa
 Systemic sclerosis
Figure 1.

 Approach to reticulate hyperpigmentation with typical onset in infancy and childhood.

Figure 2.

 Approach to reticulate hyperpigmentation with typical onset in adolescent and adult.

Reticulate hyperpigmentation with onset in infancy and childhood

Early-onset reticulate hyperpigmented disorders are usually inherited. Many conditions not only have cutaneous features but also involve other ectodermal structures and systemic organs. In addition, diseases with generalized distribution may present initially with localized patterns, and later progress to generalized distribution.

Incontinentia pigmenti is an X-linked dominant genodermatosis, which is embryonic lethal for males. It is characterized by erythema, blisters and verrucous lesions along Blaschko lines, which develop within the first few weeks of life (stages 1 and 2). Linear reticulate hyperpigmentation (stage 3) develops during infancy, persists during childhood, and fades during adolescence (Fig. 3). Atrophic hypopigmentation (stage 4) develops during adolescence and persists indefinitely. Associated conditions include scarring alopecia, nail changes, dental abnormalities, ophthalmological abnormalities and neurological abnormalities.1

Figure 3.

 Incontinentia pigmenti stage 3: reticulate hyperpigmentation along the Blaschko line. Photo courtesy of Amornsri Chunharas, MD.

Epidermolysis bullosa simplex with mottled pigmentation is characterized by localized or generalized skin blistering beginning at birth or infancy, and reticulate mottled hyperpigmentation on the trunk and proximal limbs (Fig. 4). The blistering may improve with age, whereas pigmentation progresses during childhood.

Figure 4.

 Epidermolysis bullosa simplex with mottled pigmentation: reticulate hyperpigmentation admixed with hypopigmented macules. Photo courtesy of Jemima Mellerio, MD.

Dermatopathia pigmentosa reticularis is a rare autosomal dominant disorder characterized by persistent reticulate hyperpigmentation that presents by the age of 2 years. The predilection sites are the trunk and proximal limbs. Additional features include nonscarring alopecia, onychodystrophy, absent dermatoglyphics, punctuate palmoplantar keratoderma, and hypohidrosis or hyperhidrosis. The main differential diagnosis is Naegeli–Franceschetti–Jadassohn syndrome, which is characterized by reticulate hyperpigmentation developing within the first 2 years of life, hypohidrosis, absent dermatoglyphics, diffuse and punctuate palmoplantar keratoderma, onychodystrophy, and dental anomalies. Table 2 summarizes the clinical findings of these two conditions.

Table 2.   Comparison of dermatopathia pigmentosa reticularis (DPR) and Naegeli–Franceschetti–Jadassohn syndrome (NJFS).
Clinical findingsDPRNFJS
PigmentationReticulate hyperpigmentation on the trunk, and proximal limbs; onset by 2 years of age; persists into adulthoodReticulate hyperpigmentation on the trunk, perioral and periocular areas, proximal limbs, neck, axillae, and groins; onset by 2 years of age; lesions fade after puberty
Palmoplantar keratodermaPunctatePunctate or diffuse
Dermatoglyphic linesAbsentAbsent
SweatHypohidrosis or hyperhidrosisHypohidrosis
HairNon-scarring alopeciaNormal
NailNail dystrophyNail dystrophy
TeethNormalCommon (abnormal shape, supernumerary teeth, enamel defects, tooth loss)

Dyskeratosis congenita is a rare genodermatosis with multisystemic involvement. There are three patterns of inheritance: X-linked recessive (most common), autosomal recessive and autosomal dominant. Reticulate hyperpigmentation, nail dystrophy, leucoplakia, bone-marrow failure and increased risk of malignancy (e.g. mucosal squamous cell carcinoma, leukaemia, Hodgkin disease) are the hallmarks. The hyperpigmentation is brown-grey, and may be associated with guttate hypopigmentation, telangiectasia and atrophy. Predilection sites include the neck, upper chest and upper arms. Nail changes include longitudinal ridging, splitting, pterygium and nail loss. Pigmentation and nail changes develop within the first decade, bone-marrow failure develops in the second or third decade, and malignancies develop during the third or fourth decade.2 Similar cutaneous findings have been described in Revesz syndrome, in which exudative retinopathy, retinal detachment, cerebellar hypoplasia and bone-marrow failure are associated findings.3 Dyskeratosis congenita is sometimes difficult to distinguish from Fanconi anaemia (FA), which is characterized by pigmentary changes, bone-marrow failure and predisposition to malignancy (e.g. squamous cell carcinoma, leukaemia, hepatocellular carcinoma). However, the pigmentary changes in FA are more diffuse, and café-au-lait macules may be present. Short stature and radial ray bone defects involving the thumb are associated features.4

X-linked reticulate pigmentary disorder (XLRPD, Patington syndrome type II) is an X-linked inherited disorder. In boys, generalized reticulate hyperpigmentation develops between 4 months and 5 years of age. It usually starts on the cheeks, inner thighs and buttocks. Associations include xerosis, hypohidrosis, silvery-grey or blonde unruly hair, dental anomalies, corneal clouding, delayed bone age, colitis, gastro-oesophageal reflux, recurrent pneumonia and neurological defects. In female carriers, the reticulate hyperpigmentation develops along Blaschko lines, and appears within the first few weeks of life. XLRPD is difficult to distinguish from stage 3 incontinentia pigmenti; however, there is no preceding erythema or vesicles, and no systemic association.2

In mitochondrial disorders, reticulate hyperpigmentation in photoexposed areas has been described in 3.6% of patients, often preceded by erythematous rashes. Neuromuscular abnormalities usually occur before the age of 2 years, and the onset of pigmentation ranges from 9 months to 11 years of age.5

Reticulate hyperpigmentation with onset in adolescents and adults

In late-onset reticulate hyperpigmentation, lesion distribution is an important clue to diagnosis. There are many patterns of distribution, including acral, flexural, truncal and facial; however, in some conditions, the distribution may be nonspecific.

Reticulate acropigmentation of Kitamura is characterized by reticulate, atrophic, freckle-like hyperpigmentation beginning on the dorsa of the hands and feet, without associated hypopigmentation (unlike in acropigmentation of Dohi). It is inherited in an autosomal dominant pattern, with onset in late childhood or after puberty.6 The pigmentation darkens and spreads to other sites over time. Associated findings are pits on the palms, soles, dorsal hands and feet. The histology shows epidermal atrophy, hyperpigmented elongated rete ridges and increased numbers of dopamine-positive melanocytes in the basal epidermis.

The ‘dirty neck’ sign in atopic dermatitis (AD) is characterized by reticulate ripple-like hyperpigmentation on the anterolateral neck, which affects approximately 2% of adult patients with chronic AD. The mechanisms of this condition may be due to postinflammatory pigmentary changes and ultraviolet exposure. Histopathological examination reveals eczematous changes and pigmentary incontinence.7

Dowling–Degos disease is an autosomal dominant genodermatosis characterized by reticulate hyperpigmentation on the flexures. The onset is typically in the third to fourth decade. Pigmentation is initially localized to the axillae and groins; it progresses slowly and may affect the intergluteal and inframammary folds, neck, trunk, and inner surfaces of the arms and thighs. Additional findings are perioral or facial pitted scars, dark comedone-like lesions, and epidermal cysts. The histopathology shows basal hyperpigmentation in an ‘antler-like’ pattern arising from the undersurface of the epidermis and the hair follicles. Similar patterns of pigmentation have been described in Galli–Galli disease, in which pruritic, erythematous, scaly papules on the flexures, trunk and proximal limbs are associated features. The histopathological findings are similar to Dowling–Degos disease (DDD), with additional acantholysis. Onset ranges from 15 to 56 years.8

Pigmentatio reticularis facei et colli is characterized by brown-black, atrophic, depressed reticulate, macular pigmentation on the face and neck without preceding inflammatory changes.9 The typical age of onset is 20 years. Associations include seborrhea and multiple epithelial cysts on the trunk. It may represent a variant of DDD.

If lesions occur predominately on the trunk, the differential diagnosis includes confluent and reticulate papillomatosis of Gougerot and Carteaud (CARP), prurigo pigmentosa, erythema ab igne, and Ashy dermatosis.

The mean age of onset of CARP is 18.5–21 years. Clinically, it starts as erythematous to brownish papules, 1–2 mm in size, which slowly enlarge and coalesce form lesions with a central plaque and peripheral reticulate pattern. It usually develops between the breasts and in the midline of the back, and gradually spreads over the breasts, abdomen and pubic area (Fig. 5). The histopathological findings are hyperkeratosis, acanthosis, papillomatosis, and a basal pigmentation similar to acanthosis nigricans but less pronounced.10

Figure 5.

 Confluent and reticulated papillomatosis: reticulate brownish macules with slightly hyperkeratotic surface on the intermammary region.

Prurigo pigmentosa is characterized by recurrent pruritic erythematous papules and vesicles, which resolve with reticulate hyperpigmentation (Fig. 6a,b). It usually affects adolescent and young adult female patients. Predilection sites include the back and chest. The histopathological findings of early lesions include neutrophilic infiltration around superficial blood vessels and epidermis, with epidermal spongiosis, ballooning and necrotic keratinocytes. In fully developed lesions, eosinophils and lymphocytes predominate (Fig. 6c). In the late stage, the epidermis becomes hyperplastic and parakeratotic, with lymphocytes and melanophages in the dermis.11

Figure 6.

 Prurigo pigmentosa. (a) Multiple erythematous crusted papules and papulovesicular lesions. (b) Resolved lesion of prurigo pigmentosa. (c) Scattered dyskeratotic cells, slight spongiosis, ballooning, lymphocyte exocytosis and perivascular infiltration with lymphocytes and eosinophils in the papillary dermis (haematoxylin and eosin, × 200).

Erythema ab igne is characterized by localized areas of reticulate erythema and hyperpigmentation that result from chronic heat exposure (e.g. heating pads, heating blanket, laptop computer). It is typically seen in middle-aged or older patients, and is more common in women. The distribution depends on the contact site, but is commonest on the trunk. Initial lesions are blanchable reticulate erythemas. With repeated exposure to heat, the erythema evolves into a nonblanchable dusky hyperpigmentation with epidermal atrophy. Hyperkeratosis and bullae may be seen in the late stage. The histopathological findings depend on the stage of the lesions, but epidermal atrophy, focal hyperkeratosis, dyskeratosis, squamous atypia, dermal melanin and haemosiderin pigmentation, and vasodilatation are typical. Development of squamous cell carcinoma is a possible long-term consequence.

Ashy dermatosis presents as grey-blue oval or irregularly shaped macules and patches, sometimes with a raised, erythematous border (erythema dyschromicum perstans), developing symmetrically on the trunk and proximal limbs. Numerous lesions produce a reticulate pattern of pigmentation. Most cases first appear in early adult life. The histopathological features include vacuolar degeneration of the basal cell layer, and a perivascular infiltration of lymphocytes, histiocytes and melanophages.12

Reticulate hyperpigmentation has also been reported as a pigmentary change in systemic sclerosis.13 It primarily involves the chest, abdomen and back. The skin may be slerotic. The histological findings are basal hyperpigmentation, pigmentary incontinence, and thickened and hyalinized collagen.

Diltiazem-induced hyperpigmentation is characterized as a slate-grey reticulate pigmentation without preceding inflammation on photoexposed areas (e.g. face, neck, forearms). The onset of lesions has been reported as ranging from 1.5 months to 12.5 years after exposure to diltiazem, and slowly improves after discontinuation of the drug.14 Histopathological changes include lichenoid dermatitis with pigmentary incontinence.15

Lichen planus pigmentosus is a rare subtype of lichen planus, characterized by dark-brown pigmentation without typical lesions of lichen planus.16 The mean age of onset is 34 years. Pigmentation is usually diffuse, but a reticulate pattern has been reported in 21% of cases.17 Common distribution points are the face, neck and flexural areas (Fig. 7). The histopathological findings are hyperkeratosis, atrophic epidermis, vacuolar alteration and lichenoid infiltrates in the dermis with pigmentary incontinence.

Figure 7.

 Lichen planus pigmentosus: multiple brownish macules with a smooth surface, forming hyperpigmented patches with a reticular pattern.

Postinflammatory hyperpigmentation due to various inflammatory dermatoses occasionally displays a reticulate pattern. The distribution depends on the primary lesions. Postinflammatory hyperpigmentation is the most likely diagnosis if there is a history of preceding inflammation or there is coexistence of inflammatory lesions.18

Pigmented contact dermatitis is a peculiar form of contact dermatitis characterized by unusual black or brown, diffuse or reticulate hyperpigmentation with minimal signs of inflammation. The distribution varies, depending on the contact site. It is caused by repeated invasion of a very small amount of allergens. The common allergens include fragrance, dye, optical whiteners and bactericidals. Patch testing and avoidance of causative allergens are the key steps in management.19,20

Treatment

Treatment of reticulate hyperpigmentation is often unsatisfactory. Hydroquinone, tretinoin and azelaic acid have been tried, with variable success.2 In disorders with associated inflammation, topical corticosteroids and calcineurin inhibitors may be used. Avoidance of allergen and heat is an important step in the management of pigmented contact dermatitis and erythema ab igne, respectively. Dapsone, minocycline and doxycycline have been used to treat prurigo pigmentosa.11 In CARP, minocycline and azithromycin are commonly used.10 For patients with associated systemic involvement, early detection and appropriated referral are important.

Conclusion

A practical approach to reticulate hyperpigmentation based on the typical onset of the disease is presented. Further distinction of the disorders is dependent on the distribution and associated clinical findings (e.g. signs of ectodermal dysplasia, systemic associations). Skin biopsy is helpful in some conditions. Medical history and physical examination should be used to direct further investigations in such patients.

Learning points

  •  Reticulate hyperpigmentation is a feature of numerous conditions, which can be differentiated by the typical age of lesion onset, distribution of the lesions and associated systemic involvement.
  •  Infancy and childhood-onset reticulate hyperpigmentation may be associated with hair, nail, tooth, eccrine and systemic abnormalities.
  •  The onset of inherited reticulate hyperpigmentation is usually in infancy and childhood, with the exception of Kitamura acropigmentation and DDD, for which the onset is later in life.
  •  Reticulate hyperpigmentation with onset in adolescence and adulthood is usually benign, without systemic involvement.
  •  In general, treatment of reticulate hyperpigmentation is often unsatisfactory, except in cases with identifiable causes (e.g. contact allergens, drugs, heat) and those with associated inflammation (e.g. prurigo pigmentosa, atopic dermatitis, lichen planus pigmentosus).
  •  Comprehensive examination, early diagnosis and appropriate referral are important.

Acknowledgements

I thank Drs P. Suchonwanit and S. Kanokrungsee for their assistance in the preparation of the illustrations.

CPD questions

Learning objective

To demonstrate a practical approach to reticulate hyperpigmentation based on the age of onset, distribution, associated clinical findings, and distinguishing features of each condition.

Question 1

Which one of the following diseases has its typical onset in childhood?

a) Galli–Galli disease

b) Dowling–Degos disease

c) Dermatopathia pigmentosa reticularis

d) Reticulate acropigmentation of Kitamura

e) All of the above

Question 2

Which one of the following diseases has the typical distribution on the flexural area?

a) Revesz syndrome

b) Galli–Galli disease

c) Prurigo pigmentosa

d) Confluent and reticulate papillomatosis

e) X-linked reticulate pigmentary disorder (males)

Question 3

Which one of the following clinical features distinguishes dermatopathia pigmentosa reticularis from Naegeli–Franceschetti–Jadassohn syndrome?

a) Alopecia

b) Onychodystrophy

c) Dermatoglyphic lines

d) Onset of hyperpigmentation

e) Punctate palmoplantar keratoderma

Question 4

Which of the following medications has been reported as a cause of photodistributed reticulate hyperpigmentation?

a) Diltiazem

b) Amiodarone

c) Minocycline

d) Chlorpromazine

e) Hydroxychloroquine

Question 5

Which of the following allergens is a common cause of pigmented contact dermatitis?

a) Gold

b) Nickel

c) Fragrance

d) Sunscreen

e) Formaldehyde

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