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Case Report

Prurigo pigmentosa: a case with rapid response to doxycycline and the likely pathogenetic role of neutrophils

Hui, Laura L.Y. MBBS, MRCPa,; Lee, Joyce S.S. MBBS, MRCP, FAMS, Dip. Dermpath (ICDP-UEMS)a; Tey, Hong Liang MBBS, FRCP(Edin)a,b,c

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doi: 10.1097/itx.0000000000000051
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Abstract

Case report

A 14-year-old Chinese female presented to the dermatology outpatient clinic with progressive pruritus over the upper back for the past 3 months. She had been well with no past medical history or history of crash diets. There were no identifiable preceding triggers or contactants. She was distressed by the severe itch she was experiencing and had been treated by multiple doctors with various antihistamines and potent topical steroids without any improvement.

On examination, hyperpigmented macules and patches coalescing into a reticulate pattern on the upper back was seen. These were interspersed with multiple erythematous papules (Fig. 1). Examination of her oral mucosa, flexures, and chest were unremarkable.

F1
Figure 1:
A, Reticulated hyperpigmentation on the upper back, admixed with erythematous papules. B, Marked clinical improvement after 2 weeks of oral doxycycline, with reduction of self-reported itch score from 9 to 2.5 of 10 (numerical rating scale 0–10).

A skin biopsy showed mild epidermal spongiosis with a basketweave stratum corneum and focal parakeratosis (Fig. 2A). There was a superficial perivascular infiltrate of mainly lymphocytes in association with rare neutrophils and eosinophils within the upper dermis. Occasional melanophages were present (Fig. 2B). This was clinically consistent with a late stage of prurigo pigmentosa (PP) and she was treated with oral doxycycline. On subsequent clinic review, marked clinical improvement and rapid reduction of her self-reported itch score from 9 to 2.5 of 10 over a duration of 2 weeks was observed (Fig. 1B).

F2
Figure 2:
A, Basketweave stratum corneum with focal parakeratosis and mild epidermal spongiosis. There is a superficial perivascular infiltrate of mainly lymphocytes, with rare neutrophils and eosinophils. (H&E, magnification ×100). B, Occasional melanophages and rare neutrophils are seen within the upper dermis. (H&E, magnification ×400).

Discussion

PP was described by Nagashima et al1 in 1970 as a rare dermatosis occurring most commonly in young Asian women, with the sudden onset of pruritic papules involving the trunk and neck that can progress to vesicles or pustules, which coalesce to reticulated patches. The distribution is typically symmetrical with a predilection for the posterior neck, central chest, upper back, lumbosacral area and abdomen. Rarely, asymmetric patterns with unilateral, segmental and bullous forms have been described2.

The diagnosis of PP is very challenging as various morphologies can be seen and histology findings differ depending on the stage that it is biopsied. Böer et al3 described the 4 evolving morphologic stages. Early lesions present as erythematous papules or urticarial plaques. Developed lesions can be papulovesicular or pustular. Resolving lesions tend to be crusted and scaly, while the late stages present with reticulated hyperpigmentation. The chronologic evolving nature of PP is reflected in the histopathologic findings (Table 1).

Table 1 - Clinicopathologic correlation of prurigo pigmentosa2,3.
Stage Clinical Morphology Histologic
Early Pruritic papules, plaques Basketweave stratum corneum
Erythematous—urticarial Dermal edema
Few necrotic keratinocytes
Neutrophils +/− eosinophils within the epidermis and upper dermis
Developed Papules, vesicles, pustules Epidermal spongiosis and spongiotic vesiculation
Can be crusted Necrotic keratinocytes
More prominent infiltrate of neutrophils +/− eosinophils within the epidermis and upper dermis
Basal vacuolar alteration
Lymphocytic perivascular or lichenoid infiltrate
Erythrocyte extravasation
Late Reticulate pigmentation Mild hyperkeratosis and focal parakeratosis
Perivascular lymphocytic infiltrate
Melanophages in papillary dermis

The underlying pathogenesis of PP is unknown. Several postulations have included climate changes and heat, with aggravations in spring and summer2. Mechanical forces and pigmented contact dermatitis have been implicated, but subsequent studies have not been supportive4. There have also been case reports associated with weight loss, dieting, bariatric surgery, anorexia nervosa, ketogenic diets, and diabetes mellitus5.

PP is characterized by the classical lack of response from antihistamines or topical corticosteroids. Reported efficacious treatments have mostly been antineutrophilic. Tetracyclines are typically used first-line, and they act by inhibiting the migration and function of neutrophils6,7. During the early stages of PP when neutrophils are abundant, treatment with tetracyclines may stop the disease. Minocycline is a semisynthetic tetracycline with anti-inflammatory properties and has been shown to inhibit the chemotaxis of neutrophils6. Doxycycline reduces interleukin (IL) 6 and 8, which is a neutrophil chemoattractant8. We have previously described a 16-year-old patient successfully treated with doxycycline with no subsequent recurrence9. It has also been proposed that minocycline might be more effective than doxycycline in the treatment of PP, in part due to its higher efficacy as a reactive oxygen species scavenger, with activity against IL-86. Dapsone, which inhibits the migration and function of neutrophils, has also been used.

Although patients with PP respond markedly to tetracyclines, the underlying mechanism has not been elucidated. It was previously demonstrated that PP patients had increased expression of IL-6/8 from lesional skin7, and a retrospective Taiwanese study found the presence of bacterial colonies in hair follicles of two-thirds of patients with PP (21/32), with 7 who had folliculitis and 11 with perifolliculitis, although no bacteria was identified on cultures10. Bacterial inflammation, playing a role in the pathogenesis was proposed as a possible reason for the efficacious response to antibiotics. The possible follicular bacterial involvement and neutrophilic inflammation can also correlate with observations of disease flares or higher incidences corresponding with higher temperatures and humidity, and with predilection for seborrheic areas10.

PP remains a rare condition in which pathogenesis is little known. We present a case of PP with rapid response to treatment with doxycycline, which adds to other observations supporting the important role of neutrophilic inflammation in the pathogenesis of PP.

Sources of funding

None.

Conflict of interest statement

The authors declare that they have no financial conflict of interest with regard to the content of this report.

References

1. Nagashima M, Ohshiro A, Shimizu N. A peculiar pruriginous dermatosis with gross reticular pigmentation. Jpn J Dermatol B 1971;81:38–39.
2. Beutler BD, Cohen PR, Lee RA. Prurigo pigmentosa: literature review. Am J Clin Dermatol 2015;16:533–43.
3. Böer A, Misago N, Wolter M, et al. Prurigo pigmentosa: a distinctive inflammatory disease of the skin. Am J Dermatopathol 2003;25:117–29.
4. Atasoy M, Timur H, Arslan R, et al. Prurigo pigmentosa in a patient with nickel sensitivity. J Eur Acad Dermatol Venereol 2009;23:228–30.
5. Alshaya MA, Turkamani MG, Alissa AM. Prurigo pigmentosa following ketogenic diet and bariatric surgery: a growing association. JAAD Case Rep 2019;5:504–7.
6. Ishikawa C, Tsuda T, Konishi H, et al. Tetracyclines modulate protease-activated receptor 2-mediated proinflammatory reactions in epidermal keratinocytes. Antimicrob Agents Chemother 2009;53:1760–5.
7. Gironi LC, Farinelli P, Giacalone A, et al. The efficacy of minocycline in inflammatory dermatoses: a case of prurigo pigmentosa of prepubescent onset in Western world. Dermatol Ther 2015;28:239–42.
8. Lu PH, Hui RCY, Yang LC, et al. Prurigo pigmentosa: a clinicopathological study and analysis of associated factors. Int J Dermatol 2011;50:36–43.
9. Mok YJ, Lim KS, Tey HL. Doxycycline—an emerging therapy for prurigo pigmentosa. J Eur Acad Dermatol Venereol 2012;26:526–7.
10. Kafle SU, Myint Swe S, Hsiao P-F, et al. Folliculitis in prurigo pigmentosa: a proposed pathogenesis based on clinical and pathological observation. J Cutan Pathol 2017;44:20–27.
Keywords:

Prurigo pigmentosa; Doxycycline; Neutrophil

Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The International Forum for the Study of Itch.