Nagashima (Figure 1), a Japanese dermatologist, and two of his colleagues, Oshiro and Shimizu, were the first to publish, in 1971, an account of their experience with "A peculiar pruriginous dermatosis with gross reticular pigmentation," for which they proposed the name "prurigo pigmentosa" ¹. The original article was written in Japanese and that may be the chief reason the disease seems subsequently to have been recognized more often in Japan than elsewhere. Between 1967 to 1969, Nagashima and his associates observed eight patients, all of them Japanese, who suffered from a malady that presented itself in repeatable fashion. In their seminal article they pointed out what they regarded to be characteristic features of the disease clinically, summarizing them as follows (translated from the Japanese):

". . . we accumulated eight cases of a disease which we could not diagnose and which were characterized by a highly pruritic red rash which left behind reticular pigmentation. . . . The lesions had an urticarial aspect and often were scratched. The red, highly pruritic rash tends to recur and when it remits leaves a coarse reticular pigmentation. The back, neck, and clavicular region are favorite sites. Young females are most often affected." Nagashima et al., 1971, Japanese Journal of Dermatology¹

Nagashima and his coworkers referred to the condition as "an ignored clinical entity". They illustrated the clinical features by way of 12 photographs (Figures 2A-D) that showed clearly how similar was the eruption as it presented itself in all of the patients reported on. Sections of tissue from biopsy specimens (Figures 3A-B) were seen to exhibit the following findings (translated from the Japanese):

"In biopsies taken from the rash, spongiosis, vesiculation, and exocytosis of inflammatory cells was seen. The basal cell layer showed vacuolization. The papillary dermis was edematous and contained dilated blood vessels. A dermal perivascular infiltrate consisting of lymphocytes and some neutrophils could be observed. The pigmented lesions showed pigmentation of the basal layer and a dermal perivascular infiltrate of lymphocytes." Nagashima et al., 1971, Japanese Journal of Dermatology¹

The following photographs (Fig. 2 A – D) from Nagashima"s original article in 1971 show how similar is the eruption of prurigo pigmentosa in each of his patients. Lesions are distributed somewhat symmetrically on the trunk. The upper part of the back (Fig. 2A), the neck (Fig. 2B), and the lower part of the back (Fig. 2C) are sites of predilection. In each of the photographs, the lesions can be seen to have become confluent in foci and, by virtue of that, to have assumed a reticular pattern.

The following photomicrographs (Fig. 3A and 3B) appeared in the article of Nagashima et al. in 1971.

Although Nagashima and his collaborators thought the histopathologic findings were non-specific, they classified the pruritic papules among the "pruriginous dermatoses" and suggested the name "prurigo pigmentosa" for the condition; that designation captured only the itching and the peculiar netlike pigmentation that was residual. In their judgment, the differential diagnosis included confluent reticulated papillomatosis of Gougerot and Carteaud, erythema dyschromicum perstans ("ashy dermatosis"), pigmented contact dermatitis, lichen pigmentosus, urticaria pigmentosa, and prurigo melanotica (the latter being a disorder first recorded by Pierini and Borda and associated with cirrhosis²), the link among those various maladies being marked pigmentation clinically. Nagashima et al. emphasized the uniquences of prurigo pigmentosa and stressed that all of the diseases in their differential could be excluded by virtue of attributes they deemed to be characteristic of prurigo pigmentosa. The authors sought to manage the eruption with antihistaminics, antiserotonins, and corticosteroids administered systemically, but none of those medications proved to be effective.

After the initial article by Nagashima et al., prurigo pigmentosa came to be recognized in Japan increasingly and, soon thereafter, several reports of patients affected by it appeared in the Japanese literature. By 1978, over 40 patients with prurigo pigmentosa, including those of Nagashima and his fellow workers, had been recorded. At that time, Nagashima elected to publish his findings in a forum that would attract more attention internationally. The article, in English, was published in 1978 in The Journal of Dermatology and was titled, "Prurigo pigmentosa-clinical observations of our 14 cases". The stated purpose of Nagashima was "to report on this new clinical entity. . . as no such entity has ever been noted. . . in other countries" ³. He described the clinical features of the condition in these words:

"The primary lesions of the disease are a few slightly-raised reddish papules, ranging in size from a millet seed to a half-grain of rice. . . . The papules, accompanied by severe pruritus, evolve to urticarial papular lesions by the stimulus of scratching. The size of each papule then becomes enlarged, and sometimes two or three of them coalesce. . . . These urticarial papular lesions begin to subside spontaneously in two or three days along with disappearance of the pruritus, and the conditions usually improve in about a week. However, the pigmentation is left in the lesions, and the papules may recur. . . . The pigmented spots,. . . because of repeated occurrence of the reddish papules, tend to coalesce and to show a motted, gross reticular or marble-like appearence. . . . Because of the absence of recurrences, the pigmentation gradually clears.". . .

"When repeated attacks occur in short succession, tiny excoriations, crusts and scales . . . are found. . . . Sometimes the lesions may be covered by polymorphous eczematous features." Nagashima, 1978, The Journal of Dermatology³

The findings in sections of tissue from biopsy specimens were summarized by Nagashima thus:

"Reddish papules: . . . exocytosis, inter- and intracellular edema, and liquefaction degeneration of the basal cell layer. Marked spongiosis or spongiotic bullae are not constant features. . . In the upper and middle portion of the dermis, varying degrees of edema, dilation of the blood vessels and perivascular round cell infiltration were found. . . . Pigmented lesions: . . . moderate to marked incontinence of pigments and mild perivascular round cell infiltration in the dermis." Nagashima, 1978, The Journal of Dermatology³

For Nagashima, the findings histopathologically in both the epidermis and the dermis were "non-specific and not diagnostic", which prompted him to conclude that diagnosis of prurigo pigmentosa should be made on the basis of clinical features characteristic of it.

In regard to therapy of prurigo pigmentosa, Sugawara et al. had commented in 1973, in an abstract written in Japanese, about a "dramatic response . . . in one patient [with prurigo pigmentosa to] 100 mg of diamino-diphenyl-sulfone [dapsone]"⁴. By dint of experience with four patients, Nagashima confirmed the effectiveness of dapsone in the treatment of prurigo pigmentosa, but he could not explain the mechanism of action of it, stating simply that ". . . the reason for successful treatment with DDS (diamino-diphenyl-sulfone, dapsone) is as yet unknown, [although] this drug is recommended as useful for the disease". Dobson abstracted the essence of Nagashima's article for The Year Book of Dermatology of 1979 and opined that the very good response to dapsone indicated that patients with prurigo pigmentosa probably had an unusual variant of dermatitis herpetiformis ⁵. Dobson recommended, therefore, that studies employing immunofluorescence be carried out routinely when a diagnosis of prurigo pigmentosa was suspected. No such studies had been performed by Nagashima.

Once the disease gained attention through publications about it in journals whose readership was international, and especially after Coterill and his coworkers, in the British Journal of Dermatology in 1981, shared their experience with two patients with prurigo pigmentosa, those being the first with the disease remarked on in the West ⁶, the number of reports of the condition in other countries began to increase, albeit slowly. An article by Teraki, Nagashima, and other Japanese colleagues appeared in the British Journal of Dermatology in 1991 ⁷, and it received more attention than had been given the original one in English by Nagashima in 1978. Whereas only six non-Japanese patients with prurigo pigmentosa were identified in the decade before 1992, 18 non-Japanese patients have come to notice as of today, an indication that the disease is more prevalent outside Japan than was thought previously. The non-Japanese patients were said to be Chinese^8,9, Tunesian^10,11, western European^6,12,13, middle European^14,15, Italian^16–18, Portuguese¹⁹, Spanish²⁰, Moroccan²¹, Turkish²², and both Caucasian^23,24 and African Americans²⁵ living in the United States. Interestingly, five of the non-Japanese patients were Sicilian, and three of them had been diagnosed incidentially in the course of an undertaking devoted to "Skin pathology findings in a cohort of 1500 adult and elderly subjects"²⁶ Siragusa and Schepis, who studied the Sicilian patients, speculated that prurigo pigmentosa might be a disease that was more common than appreciated but underdiagnosed, or a disease of Sicilians especially.

In little more than 30 years, over 200 patients with prurigo pigmentosa have been reported on in Japan, many of them in presentations at conferences (as evidenced by a search in Centra Revuo Medicine, Japan). In the literature of dermatology written in Japanese, more than 70 patients have been presented since Nagashima's original article appeared in 1971. Preponderance of Japanese patients in the literature given to prurigo pigmentosa is more explicable on the basis of greater awareness of the disease in Japan than on ethnologic proclivity of the disease for Asians.

The fact that prurigo pigmentosa is diagnosed rarely in the West is evident by even casual perusal of most standard textbooks of dermatology, dermatopathology, and general pathology, only few of which even mention the disorder^27–30, and half of those that do refer to it make no reference to Nagashima's publications in 1971 and 1978^29,30. A clinical photograph of the disease was pictured in only one volume, that is, the Textbook of Dermatology edited by Rook, Wilkinson, and Ebling²⁷. Histopathological findings of prurigo pigmentosa are given short shrift, no more than a paragraph, in the forementioned textbooks and, in general, are said to be those of a non-specific, somewhat lichenoid tissue reaction with a superficial perivascular infiltrate of lymphocytes mainly, interface changes, and, in hyperpigmented lesions, melanophages.

At the 22nd Colloquium of the International Society of Dermatopathology that convened in Stresa, Italy, in October 2001, a question was raised about whether prurigo pigmentosa truly is a distinct entity, clinically and histopathologically. The work presented here was joined in an effort to answer that question. The new observations that follow are based on study of 25 patients with prurigo pigmentosa, most of whom had numerous exacerbations and recurrences of the disease over the course of up to 10 years. A review of the subject that then follows concerns 178 patients of more than 10 nationalities and includes every patient who has been reported on to date in the medical literature of the English language (search by medline), as well as the vast majority of patients published in the literature of dermatology written in Japanese.