Doxycycline an emerging therapy for prurigo pigmentosa

group: 25–34, 4.0%), but occurred earlier in women (age group: Comparisons with data from paediatric cross-sectional studies, showed that the relative prevalence of SD in Greek outpatient chil- dren aged 0–15 years (2.5%) was lower than that in Indian8 Prurigo pigmentosa is a rare, idiopathic inflammatory dermatosis (11.3%) and Chinese9 (3.2%) children, whereas in adults (4.05%), that was first reported in Japan in 1971.1 It is characterized by an it was lower than Chinese9 (7%), similar to Iranian10, and higher initial eruption of pruritic macules and papules, which subse- than British populations5 (2.35%) (Table 2).
quently evolves into a reticulate pattern of hyperpigmentation Finally, when making geographical comparisons of the available crude male-to-female ratio (1.04, 1039 ⁄ 996, Table 1), a lower male Minocycline and dapsone have most frequently been reported morbidity was found when compared to a British series5 (1.47, to successfully treat prurigo pigmentosa.3,4 Both drugs work by 958 ⁄ 652) and almost similar morbidity to an Iranian series10 inhibiting the migration and function of neutrophils. A prominent adverse drug reaction from minocycline use is the development ofhyperpigmentation, which has an estimated incidence of 3–5%.5 I. Palamaras,† K.P. Kyriakis,‡,* N.G. Stavrianeas§ Although cessation of minocycline therapy often results in resolu- Department of Dermatology, Barnet & Chase Farm NHS Trust tion of the hyperpigmentation, the signs may persist and can be Hospitals, London, UK, ‡Department of Dermatology & Venereology, West Attika General Hospital, ‘‘H Agia Varvara’’, Athens, Greece and severe. On the other hand, dapsone poses the risks of haemolytic §2nd Department of Dermatology & Venereology, ‘‘ATTIKON’’ anaemia, agranulocyctosis and hepatocellular damage. Its use requires screening for glucose-6-phosphate dehydrogenase defi- *Correspondence: Dr K.P. Kyriakis. E-mail: fountou@otenet.gr ciency and monitoring of full blood counts and liver function.
Tetracycline has also been tried, but studies have shown conflict- ing results.6 Other drugs that have been used with varying success include potassium iodide, sulphamethoxazole, macrolides such asclarithromycin and roxithromycin, as well as isotretinoin.
More recently, doxycycline, which is also known to have anti- 1 Naldi L, Rebora A. Clinical practice. Seborrheic dermatitis. N Engl J inflammatory properties, has emerged as a potentially promising therapeutic for prurigo pigmentosa.7 We hereby report a patient 2 Rothman K. Stratified analysis. In Modern Epidemiology. Little Brown, with prurigo pigmentosa who was successfully treated with doxy- 3 Nanda A, Al-Hasawi F, Alsaleh QA. A prospective survey of pediatric cycline, providing further support for the use of this drug in this dermatology clinic patients in Kuwait: an analysis of 10 000 cases.
Pediatr Dermatol 1999; 16: 6. PubMed-11.
Our patient, a 16-year-old Chinese girl, was presented to our 4 Tamer E, Ilhan MN, Polat M, Lenk N, Alli N. Prevalence of skin diseases among pediatric patients in Turkey. J Dermatol 2008; 35: 413.
centre with a 4-year history of a recurrent pruritic rash. The rash was triggered by excessive sweating during sporting activities and 5 Ratzer MA. The incidence of skin diseases in the West of Scotland.
would persist for months, as long as she engaged in physical activ- Br J Dermatol 1969; 81): 456. PubMed-461.
ity. She had been otherwise well and there was no personal or fam- 6 Plunkett A, Merlin K, Gill D, Zuo Y, Jolley D, Marks R. The frequency of common nonmalignant skin conditions in adults in central Victoria, ily history of atopic diathesis. Examination revealed scattered Australia. Int J Dermatol 1999; 38: 901. PubMed-908.
erythematous papules on the entire back and chest and the pres- 7 Johnson M-L, Roberts J. Skin conditions and related need for ence of a reticulate hyperpigmentation on the upper back (Fig. 1).
medical care amongpersons 1–74 years. United States, 1971–1974.
Vital Health Stat 1978; 11. U.S. Department of Health, Education The nails, flexures and mucous membranes were unaffected.
Biopsy findings revealed mild epidermal acanthosis, mild 8 Sardana K, Mahajan S, Sarkar R et al. The spectrum of skin spongiosis associated with neutrophilic and eosinophilic exocyto- disease among Indian children. Pediatr Dermatol 2009; 26: 6.
sis, and occasional apoptotic keratinocytes (Fig. 2). There was 9 Goh CL, Akarapanth R. Epidemiology of skin disease among children mild upper dermal oedema and a superficial perivascular infiltrate in a referral skin clinic in Singapore. Pediatr Dermatol 1994; 11: 125.
that was mainly lymphocytic, with occasional neutrophils and eosinophils. Occasional melanophages were also visible within the 10 Baghestani S, Zare S, Mahboobi AA. Skin disease patterns in Hormoz- gan, Iran. Int J Dermatol 2005; 44: 641. PubMed-645.
The clinical and pathological findings were consistent with a diagnosis of prurigo pigmentosa. She was commenced on doxycy-cline at 100 mg twice a day for a month. Her pruritic symptomsimproved rapidly and resolved within 1 month, although the Journal of the European Academy of Dermatology and Venereology ª 2011 European Academy of Dermatology and Venereology PAR-2 mediation.9 In our patient, there was a rapid resolution initch symptoms and subsequent progressive resolution of rashesupon initiation of doxycycline; antagonism of PAR-2 may possiblyhave a role.
In a recent case series in Taiwan, Lu et al. reported that doxycy- cline at 200 mg ⁄ day for 1–5 weeks provided good response in alltheir 16 patients.10 Our patient further demonstrated a similarpositive response. Although minocycline and dapsone have beenthe mainstays of treatment in prurigo pigmentosa, doxycyclineoffers an appealing and effective alternative with its more favour-able side effect profile.
National Skin Centre, 1 Mandalay Road, 308205 Singapore Figure 1 Scattered erythematous papules seen on the upper *Correspondence: H.-L. Tey. E-mail: teyhongliang111@yahoo.com back with a reticulate pattern of hyperpigmentation.
1 Nagashima M. Prurigo pigmentosa – clinical observations of our 14 2 Boer A, Asgari M. Prurigo pigmentosa: an underdiagnosed disease? Indian J Dermatol Venereol Leprol 2006; 72: 405–409.
3 Chiam LY, Goh BK, Lim KS, Ng SK. Prurigo pigmentosa: a report of two cases that responded to minocycline. Clin Exp Dermatol 2009; 34:e584–e586.
4 Matsumoto C, Kinoshita M, Baba S, Suzuki H, Kanematsu S, Kanema- tsu N. Vesicular prurigo pigmentosa cured by minocycline. J Eur AcadDermatol Venereol 2001; 15: 354–356.
5 Dereure O. Drug-induced skin pigmentation. Epidemiology, diagnosis and treatment. Am J Clin Dermatol 2001; 2: 253–262.
6 Baykal C, Buyukbabani N, Akinturk S, Saglik E. Prurigo pigmentosa: not an uncommon disease in the Turkish population. Int J Dermatol2006; 45: 1164–1168.
7 Ekmekci TR, Altunay IK, Koslu A. Prurigo pigmentosa treated with doxycycline. Dermatol Online J 2006; 12: 9.
8 Steinhoff M, Neisius U, Ikoma A et al. Proteinase-activated receptor-2 mediates itch: a novel pathway for pruritus in human skin. J Neurosci2003; 23: 6176–6180.
Figure 2 Mild epidermal acanthosis with neutrophilic and eosin- 9 Ishikawa C, Tsuda T, Konishi H, Nakagawa N, Yamanishi K. Tetracy- ophilic exocytosis, and occasional apoptotic keratinocytes. Mild clines modulate protease-activated receptor 2-mediated proinflammato- upper dermal oedema and a superficial perivascular infiltrate that ry reactions in epidermal keratinocytes. Antimicrob Agents Chemother was mainly lymphocytic, with occasional neutrophils and eosin- ophils (haematoxylin and eosin, ·40).
10 Lu PH, Hui RC, Yang LC, Yang CH, Chung WH. Prurigo pigmentosa: a clinicopathological study and analysis of associated factors. Int JDermatol 2011; 50: 36–43.
rashes improved gradually over few months. She had no furthernew eruptions and at a 5-month review, only a fading patch of In our patient, it is interesting to note that her disease was trig- gered only by excessive sweating during sporting activity, and thisbears similarity to aggravation of atopic dermatitis and itch after exercise and sweating. Proteinase-activated receptor-2 (PAR-2) has been found to be increased in the epidermis in atopic dermatitislesions, and PAR-2 has been found to play an essential role in the transmission of itch.8 In a recent study in keratinocyte cultures, Ishikawa et al. examined the effect of tetracyclines on the produc-tion of interleukin 8 (IL-8), the latter being an important chemo- attractant for neutrophils. It was shown that levels of IL-8 were Eosinophilic pustular folliculitis (EPF), first described by Ofuji decreased by minocycline, doxycycline and tetracycline through et al.,1 is characterized by recurrent clusters of pruritic, follicular, Journal of the European Academy of Dermatology and Venereology ª 2011 European Academy of Dermatology and Venereology

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