Prurigo Pigmentosa

Nada Shaker; Nishad Sathe

Prurigo Pigmentosa

Author: Nada Shaker Editor: Nishad C. Sathe Updated: 1/11/2024 2:25:46 AM

Introduction

Prurigo pigmentosa, also known as Nagashima disease or "keto rash," is a rare inflammatory skin disease initially described by Nagashima et al in 1971.[1] Prurigo pigmentosa typically, but not exclusively, affects young females of East Asian ethnicity, presenting as a symmetrical eruption of urticarial papules on the neck, chest, and back.[2][3] The papular eruption typically coalesces into a reticulated pattern that repeatedly resolves and recurs, resulting in hyperpigmented skin of cosmetic concern.[4] Prurigo pigmentosa can be triggered by metabolic derangements, including those secondary to ketogenic diets, which have experienced a rise in popularity in recent years. This activity reviews the proposed etiology, pathogenesis, clinical evaluation, and therapeutic management of prurigo pigmentosa and highlights the role of the interprofessional team in improving outcomes for patients with this rare dermatosis.

Etiology

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Etiology

The etiology of prurigo pigmentosa is unclear. It has been theorized that prurigo pigmentosa can be triggered by metabolic disorders, dietary modifications, hormonal changes, or infections.[5]

Prurigo pigmentosa has been linked to ketoacidosis, fasting, calorie restriction, and carbohydrate restriction, particularly in a ketogenic diet. Several reports have suggested a link between flares of prurigo pigmentosa and a serum ketone body measurement greater than 0.6 mmol/L, with the dermatosis resolving as urinary ketone levels correct. Additional studies are necessary to elucidate this connection further.[6]

Some cases of prurigo pigmentosa have occurred during pregnancy.[7][8] Prurigo pigmentosa has been reported following a COVID-19 vaccine.[9] Other studies suggest an association between prurigo pigmentosa and specific human leukocyte antigens.[10]

Epidemiology

Prurigo pigmentosa was first described in a Japanese woman. Since this initial description, prurigo pigmentosa has been reported in patients from Europe, the United States, and other countries.[1] While most commonly described in patients of East Asian ethnicity, there is no obvious reason for an ethnic preference; it has been proposed that this tendency is due to a lack of clinical awareness of this disease outside of East Asia.[11] However, mis- and underdiagnosis are frequent, and epidemiological studies reflect this. Prurigo pigmentosa is most commonly described in young women in late adolescence or early adulthood.[1][12]

Pathophysiology

The pathogenic and pathophysiologic mechanisms of prurigo pigmentosa remain unclear; research is ongoing.[8] It is hypothesized that when a susceptible person enters a ketotic state through fasting, ketoacidosis, or while on a ketogenic diet, prurigo pigmentosa develops via as yet unknown mechanisms. It has been demonstrated that a persistent ketotic state delays the healing of this dermatosis and that increasing carbohydrate consumption promotes its resolution.[13]

Additionally, it has been proposed that the chronic inflammation associated with prurigo pigmentosa may activate melanocytes to produce excess melanin, the dermal deposition of which results in persistent hyperpigmentation.[1] Postinflammatory melanin synthesis or impaired melanosome degradation may also contribute to persistent hyperpigmentation.[14]

Histopathology

Prurigo pigmentosa is typically a clinical diagnosis. However, skin biopsies are essential to rule out other disease mimickers.[15] The histopathological features of prurigo pigmentosa will vary with the stage of the disease.[16]

In the initial stages of the disease, the epidermis exhibits focal epidermal eosinophilic spongiosis, contributing to early papule formation (see Image. Prurigo Pigmentosa, 40X Magnification).[12] Intraepidermal vesicles may be seen, but these rarely become pustular. Edema may be present in the papillary dermis, and patchy lichenoid proliferation of inflammatory cell infiltrates may be observed. A mixed superficial perivascular inflammatory infiltrate comprising lymphocytes, neutrophils, and eosinophils may be noted in the upper dermis, extending to involve the dermal papillae. Vacuolar interface changes, necrotic keratinocytes, and focal epidermal necrosis are commonly noted.[17] A key histopathologic feature of prurigo pigmentosa is dermal-based dense inflammatory infiltrates of lymphocytes, histiocytes, and eosinophils; this finding may be linked to prior infectious processes, such as Helicobacter pylori.[18]

Histopathological changes commonly seen in the later stages of prurigo pigmentosa include lymphocytic infiltrates, the presence of melanophages, and pigmentary incontinence (see Image. Prurigo Pigmentosa, 100X Magnification).[12] Advanced stages of the disease exhibit a mildly hyperplastic epidermis with parakeratosis and basal hyperpigmentation (see Image. Prurigo Pigmentosa, 200X Magnification).[4]

History and Physical

The clinical examination of patients with prurigo pigmentosa reveals pruritic erythematous papules, papulovesicles, and vesicles in a symmetric and reticular pattern, predominantly on the back, upper chest, and neck (see Image. Early Stage Prurigo Pigmentosa).[1][12] The erythematous papules spontaneously evolve into hyperpigmented reticulated patches or plaques (see Image. Prurigo Pigmentosa, Late Stage). The forehead, the arms, or the abdomen are rarely affected; mucous membrane involvement is unlikely (see Image. Prurigo Pigmentosa, Hyperpigmentation).[15] Recurrences favor previously affected anatomical sites. Presentations of unilateral, segmental, bullous, or exfoliative skin lesions have been reported, albeit rarely.[19][20][21][22]

Evaluation

Laboratory testing is sometimes warranted to determine the underlying risk of developing prurigo pigmentosa and exclude an underlying clinical condition.[6][23][24][23] Laboratory evaluations that aid in identifying patients with ketoacidosis include but are not limited to:

Serum electrolytes
Serum glucose
Serum insulin
Serum ketones, including beta-hydroxybutyrate
Urinalysis
HbA1c

Treatment / Management

Most cases of prurigo pigmentosa resolve spontaneously. Medical therapy is required to achieve resolution for some patients. Addressing predisposing medical conditions is essential to disease management.

The standard therapeutic approach to prurigo pigmentosa includes oral tetracycline or macrolide antibiotics.[25] An oral minocycline regimen of 100 mg orally twice daily for 2 to 4 weeks is the preferred initial therapy; tetracyclines inhibit inflammatory cytokines, including interleukins 1 and 6, and inhibit neutrophil chemotaxis.[12][26][27][28] Macrolides are a viable antimicrobial therapy. Dapsone, a sulfone, has also demonstrated therapeutic efficacy for prurigo pigmentosa; the mechanism of action is thought to be inhibition of neutrophil chemotaxis.[26][29][30](A1)

Adjunctive topical therapies for prurigo pigmentosa include corticosteroids or calcineurin inhibitors.[31] These topical agents aid in alleviating the symptomatic pruritus associated with prurigo pigmentosa.[32] The benefits of topical dapsone and topical minocycline remain questionable.

Colchicine inhibits neutrophil chemotaxis and has demonstrated therapeutic benefit for prurigo pigmentosa.[33] Dietary modification is warranted for patients following a ketogenic diet or in patients from countries with a high prevalence of ketosis-inducing diets.[34] In susceptible individuals, the resolution of skin lesions with dietary modification supports the diagnosis of prurigo pigmentosa and guides the treatment plan for high-risk patients.[13][35](B3)

There is no known definitive treatment for persistent hyperpigmentation secondary to prurigo pigmentosa. However, topical agents, laser therapy, chemical peels, microdermabrasion, intensed pulsed light treatments, and narrowband UV-B phototherapy have been employed with varying success.[36][37][36] One study noted improvement in hyperpigmentation with Q-switched double-frequency 532-nm Nd:YAG laser therapy.[38] Hydroquinone, retinoids, and corticosteroids are the most commonly utilized topical agents.[39][40] Adjunctive measures, including strict sun protection, may also help to alleviate the visible sequelae of prurigo pigmentosa; prolonged sun exposure may worsen existing pigmentation.[41] (B3)

Differential Diagnosis

The misdiagnosis of prurigo pigmentosa is believed to be common. The most common diagnostic pitfalls of prurigo pigmentosa include confluent and reticulated papillomatosis, atopic dermatitis, and contact dermatitis.[42][43][42][44] Dermatitis herpetiformis may easily be confused with prurigo pigmentosa; however, biopsy does not commonly demonstrate ballooning and spongiosis.[1] Cutaneous lupus erythematosus may mimic prurigo pigmentosa despite the absence of spongiosis, spongiotic vesicles, and neutrophilic infiltrates in the upper epidermis. However, other mimickers of prurigo pigmentosa include but are not limited to:

lichen planus pigmentosus
dermatitis herpetiformis
bullous lichen planus
acanthosis nigricans
tinea versicolor
terra firma-forme dermatosis
febrile pityriasis lichenoides et varioliformis acuta (Mucha-Habermann disease)
Darier disease
Dowling-Degos disease
Galli-Galli disease
primary cutaneous amyloidosis
erythema ab igne

Prognosis

Most cases of prurigo pigmentosa have a favorable prognosis with no dangerous sequelae. However, residual hyperpigmentation may persist for prolonged periods and be a cosmetic concern; early treatment reduces the risk of prolonged hyperpigmentation.[45][46]

Complications

Prurigo pigmentosa is an inflammatory skin condition with no known clinical complications.

Deterrence and Patient Education

Patient education for prurigo pigmentosa includes describing the common symptoms of prurigo pigmentosa, illustrating the recurrent nature of the disease, and explaining the contributing or triggering factors that may worsen symptoms.[12] Discussing potential triggers such as fasting and carbohydrate-restricted diets in addition to appropriate control of diabetes mellitus is essential to avoid the recurrence of the disease.[6][13] It should be stressed that the lesions are not contagious.

Enhancing Healthcare Team Outcomes

Prurigo pigmentosa is a rare dermatologic inflammatory disorder characterized by distinctive clinical and histopathological features. It is often associated with intense pruritus, which can cause skin irritation and excoriations, causing significant distress and discomfort for patients. Many cases of prurigo pigmentosa are related to metabolic derangements, and collaboration between primary care practitioners, dermatologists, diabetologists, and endocrinologists facilitates the management and resolution of the disorder. Comprehensive patient education employing nurses and pharmacists ensures a holistic approach to patient care.

Media

(Click Image to Enlarge)

Early stage prurigo pigmentosa. This image depicts an early stage of prurigo pigmentosa in a young woman who presented with a recurrent symmetrically distributed pruritic eruption on the chest and back.