Histopathologic Findings

 
The findings of authors who, after Nagashima's original article in 1978, reported on changes in sections of tissue from specimens of prurigo pigmentosa are communicated in the quotations, verbatim, that follow.
 
". . . a small focus of epidermal thinning, marked parakeratosis, focal spongiosis, dermal papillary edema, dilation of superficial blood vessels and perivascular lymphocyte cuffing. Moderate numbers of melanin laden macrophages . . . " Cotterill et al., 1981, British Journal of Dermatology6
 
". . . mild hyperkeratosis . . . and an increase of melanin granules in the basal cell layer"
 
". . . mild acanthosis, elongation of the rete ridges, . . . partial spongiform edema, exocytosis and liquefaction degeneration of the basal cell layer, . . . increase in melanophages" Yamasaki et al., 1981, The Journal of Dermatology31
 
". . . intercellular edema, liquefaction degeneration of the basal layer and neutrophlic exocytosis. In the atrophic epidermis, necrosis with abscess formation and numerous dyskeratotic cells were observed. There was a moderate perivascular neutrophilic infiltration in the early biopsy and a lymphohistiocytic infiltration in the second biopsy. Pigment laden macrophages were numerous." Harms et al., 1986, Dermatologica12
 
". . . hyperkeratosis, a decreased stratum granulosum, mild spongiosis, large numbers of dyskeratotic keratinocytes throughout the epidermis, focal liquefaction degeneration of the basal layer, pigmentary incontinence, and a superficial perivascular lymphoid infiltrate" Cox et al., 1987, British Journal of Dermatology8
 
"moderate regular acanthosis with a superficial and mid-dermal perivascular mononuclear cell infiltrate. There were mild intercellular edema and parakeratosis. While the granular layer was focally diminished, hypogranulosis was not prominent. . . . moderate exocytosis of small round mononuclear cells . . . mild basal vacuolation, dyskeratosis and papillary dermal melanophages. The perivascular infiltrate contained eosinophils" Joyce et al., 1989, Archives of Dermatology23
 
"Four stages . . . Urticarial papules: . . . slight spongiosis, migration of neutrophils and slight degeneration of the basal layer . . . urticarial erythema: . . . marked spongiosis, infiltration of lymphocytes, many dyskeratotic cells and liquefaction degeneration of the basal cell layer . . . dilatation of superficial blood vessels and perivascular round cell infiltration . . . Erythema with pigmentation: . . . acanthosis. . . deposits of melanin in the upper dermis. . . reticular pigmentation:. . . marked incontinence of pigments and mild perivascular round cell infiltration in the upper dermis." Arai et al., 1992, American Journal of Dermatopathology89
 
". . . focal spongiosis, exocytosis of mononuclear cells, focal liquefaction degeneration of the basal cell layer, dyskeratotic keratinocytes and a perivascular infiltrate of lymphoid cells. . . . exocytosis of neutrophils and subcorneal abscesses were also observed in an early lesion" Sakamoto et al., 1992, European Journal of Dermatology46
 
"Stage I: Urticarial papules: epidermis: mild spongiosis, mild infiltrate of neutrophils; dermis: superficial infiltrate of neutrophils, superficial and mid-dermal infiltrate of lymphocytes. Stage II: Urticarial erythema: epidermis: epidermal hyperplasia, microabscesses, spongiosis, vesicles, dyskeratotic cells, liquefaction degeneration of the basal cell layer; dermal: elongation of rete ridges, dilatation of vessels, dermal infiltrate consisting of lymphocytes and eosinophils. Stage III: Pigmented erythema: epidermal: . . . dyskeratotic cells, dermal: melanophages, dilatated blood vessels, mild infiltrate of lymphocytes. Stage IV: . . . . Dermal melanophages" Fujita et al.,1994, Nishinihon Hifuka (translated from the Japanese) 51
 
". . . spongiotic vesicles and perivascular lymphohistiocytic infiltrate in the upper dermis." Murao et al., 1996, British Journal of Dermatology34
 
Nagashima et al., in their original publication about prurigo pigmentosa, noted only "nonspecific" findings histopathologically. This was true, too, for other authors who commented on changes in sections of tissue as they were scrutinized by conventional micoscropy. In the articles reviewed by us, biopsy specimens were obtained from 153 patients with prurigo pigmentosa and the findings encountered most often in sections of tissue were said to be these: "acanthosis" (44/153), "spongiosis" (104/153), "spongiotic vesicles" (34/153) "necrotic keratinocytes" (66/153), "intraepidermal lymphocytes" (71/153), "lymphocytes at the dermo-epidermal junction" (56/153), "liquefaction degeneration of the basal layer" (63/153), "perivascular lymphoid infiltrate in the upper dermis" (148/153), "dilatation of superficial blood vessels" (46/153), "papillary edema" (45/153) and "pigmentary incontinence" (89/153). "Necrosis" of parts of the epidermis was noted in lesions from but a few patients (7/153: 8,12,39,40,44,57,66). "Hyperpigmentation of the basal layer" of the epidermis was observed in 6 of 153 patients.6,16,31,45,53
 
Only a few of the articles addressed the matter of the chronologic sequence1,3,12,19,32,33,40,46,51,64,89 of changes in individual lesions of prurigo pigmentosa as they were judged histopathologically. Nagashima et al., in their article written in Japanese in 1971, recorded "spongiosis", "vesiculation", "exocytosis" and a dermal infiltrate of lymphocytes and a few neutrophils in early lesions,1 whereas in Nagashima's article written in English in 1978,3 "liquefaction degeneration of the basal layer" was stressed as being striking in early lesions and "pigmentary incontinence" in later ones. The latter findings were what prompted him to characterize the histopathological changes "lichenoid". Signs of lichenoid infiltration were remarked on by several authors subsequently,8,9,21,23,25,33,59,83 though other observers noted fewer changes at the dermo-epidermal interface than did Nagashima.6,23
 
Photomicrographs of prurigo pigmentosa that have appeared in published articles are pictured now in Figs. 14 A–I. The diversity of changes histopathologically is related directly to the dynamic of the process, which is extraordinary. The findings in the photomicrographs are arranged in what we regard to be the sequence of changes as a lesion of the disease develop over time, that chronological course being either very rapid (14 A-E) or much less rapid (F-I).

View Figure  		Fig. 14A  Prurigo pigmentosa. This spongiotic dermatitis with neutrophils and an edematous papillary dermis was shown in a photomicrograph that appeared in the article by Fujita et al. in 1994. The authors designated these changes "Stage I" of the disease. (Reproduced with permission from Fujita Y, Kasuoka K, Arai A, Iwasaki M: Prurigo pigmentosa—Statistical examination of 23 cases based on the histological and immunhistochemical studies, Nishinihon Hifuka 1994; 56(4):749–757).

View Figure  		Fig. 14B  Prurigo pigmentosa. This spongiotic dermatitis with neutrophils is associated with obscuration of the dermo-epidermal junction by both inflammmatory cells and vacuolar alteration. The epidermis is topped by a normal cornified layer whose configuration is basket woven, an indication that the changes pictured here are at an early phase in the process. The photomicrograph comes from the article by Harms et al. in 1986. (Reproduced with permission from Harms M, Mérot Y, Polla L, Saurat JH: Prurigo pigmentosa: 3rd non-Japanese case, Dermatologica 1986;173:202–204).

View Figure  		Fig. 14C  Prurigo pigmentosa. In addition to a superficial perivasular and interstitial infiltrate composed largely of neutrophils but also of lymphocytes, there are marked edema of the papillary dermis, prominent spongiosis, intraepidermal abscesses, and epidermal hyperplasia. That the process is early in its course can be told by a cornified layer that still is normal. These findings were pictured by Sakamoto et al. in 1992. (Reproduced with permission from Sakamoto T, Tokura Y, Tikigawa M: Prurigo pigmentosa, a case report with immunhistological observations, Eur J Dermatol 1992;2:161–163).

View Figure  		Fig. 14D  Prurigo pigmentosa. A spongiotic vesicle that houses neutrophils, nuclear "dust" of neutrophils, and lymphocytes is apparent in the lower half of the epidermis, and above it the number of necrotic keratocytes is so great that the upper half of the epidermis is nearly entirely necrotic. The papillary dermis is severely edematous. Because the cornified layer is normal these changes must have evolved very rapidly. This photomicrograph was shown by Omichi and coworkers in 1999. (Reproduced with permission from Omichi M, Kuramochi A, Tsuchida T: A case of prurigo pigmentosa with bulla formation, Rinsho Derma (Tokyo) 1999;41:1901–1904).

View Figure  		Fig. 14E  Prurigo pigmentosa. The vesicle that houses lymphocytes mostly, but also neutrophils and some "dust" of them, came into being by virtue of extensive spongiosis and slight ballooning. The upper part of the epidermis is necrotic. These changes were depicted by Matsunaga et al. in 1989. (Reproduced with permission from Matsunaga J, Hattyoume N, Tagami Y: Prurigo pigmentosa with intraepidermal vesicles containing many dyskeratotic cells and neutrophils, Rinsho Derma (Tokyo) 1989;31:273–276).

View Figure  		Fig. 14F  Prurigo pigmentosa. The character of the inflammatory cells pictured cannot be assessed accurately in this photomicrograph, but those cells are present around venules of the superficial plexus and in the slightly spongiotic, hyperplastic epidermis, where they are joined by numerous necrotic keratocytes disposed as solitary units and arranged in clusters. Note also the presence of parakeratosis. The photomicrograph appeared in an article by Cox in 1987 (Reproduced with permission from Cox NH: Prurigo pigmentosa, Br J Dermatol 1987;117:121–124).

View Figure  		Fig. 14G  Prurigo pigmentosa. Lymphocytes are situated around venules of the superficial plexus, along the dermo-epidermal junction, and within an epidermis that contains scant spongiosis but many necrotic keratocyes as solitary units, in clusters, and, in foci, en masse. Besides the basket-woven appearance of the cornified layer, there is a focus on the right of parakeratosis. This picture accompanied the publication of Teraki et al. in 1991 (Reproduced with permission from Teraki Y, Shiohara T, Nagashima M, Nishikawa T: Prurigo pigmentosa: role of ICAM-1 in the localization of the eruption, Br J Dermatol 1991;125:360–363).

View Figure  		Fig. 14H  Prurigo pigmentosa. This interface dermatitis associated with spongiosis, ballooning, many necrotic keratocytes, and mounds of parakeratosis resembles closely changes of pityriasis lichenoides et varioliformis acuta (Mucha-Habermann-disease), but the fact that the dermal infiltrate is made up of neutrophils, as well as lymphocytes, compels to a diagnosis of prurigo pigmentosa. This illustration appeared in an article by Dijkstra et al in 1987. (Reproduced with permission from Dijkstra JWE, Bergfeld WF, Taylor JS, Ranchoff RE: Prurigo pigmentosa - a persistent lichenoid reaction to bismuth? Int J Dermatol 1987;26(6):379–381).

View Figure  		Fig. 14I  Prurigo pigmentosa. Melanophages in number in the upper part of the dermis beneath a slightly hyperplastic epidermis are indicative of a lesion that has involuted largely. Fujita et al., who pictured these findings in 1994, thought that they represened "Stage IV" of the disease. (Reproduced with permission from Fujita Y, Kasuoka K, Arai A, Iwasaki M: Prurigo pigmentosa-Statistical examination of 23 cases based on the histological and immunhistochemical studies, Nishinihon Hifuka 1994; 56(4):749–757).
 
Arai et al., in 1991, presented a poster at the 12th Colloquium of the International Society of Dermatopathology in Lübeck, Germany, in which they called attention to neutrophils in the epidermis as being typical of the earliest lesion in 19 patients with prurigo pigmentosa.89 Already in 1986, Harms et al. had noted neutrophils in the epidermis of early lesions of prurigo pigmentosa12 (see Fig. 14B), but they interpreted the findings as being "nonspecific." In 1989 Matsumaya et al. found neutrophils and eosinophils, as well as subcorneal pustules, in the epidermis of a patient with prurigo pigmentosa39 and, in 1992, Sakamoto et al.46 (see Fig. 14C) stated that "marked infiltration of neutrophils into the epidermis seems to be a characteristic feature of the early prurigo pigmentosa". Despite that acknowledgement, those coworkers designated the reaction "lichenoid" histopathologically.
 
In 1994, Fujita and Arai et al. wrote again of their findings histopathologically in 23 patients with prurigo pigmentosa, this time in the Japanese journal Nishinihon Hifuka (The Nishinion Journal of Dermatology)51 (see Fig. 14 A). Early lesions, which the authors called "Stage I" of the disease, were described by them as showing mild spongiosis, a mild infiltrate of neutrophils in the epidermis, and an infiltrate of neutrophils in the superficial dermis. What the authors termed "Stage II" of prurigo pigmentosa was characterized by epidermal hyperplasia, microabscesses, spongiosis, vesicles, dyskeratotic cells, liquefaction degeneration of the epidermal basal layer, elongation of rete ridges, dilation of vessels, and an infiltrate in the dermis that consisted of lymphocytes and eosinophils. In later lesions, dubbed by them "Stage III", they told of dyskeratotic cells in the epidermis and of melanophages, dilated blood vessels, and a mild infiltrate of lymphocytes in the dermis, and in still later lesions, "Stage IV", of melanophages only in the dermis (see Fig. 14I).
 
A few neutrophils in the dermal infiltrate of "early lesions" of prurigo pigmentosa were recognized not only by Nagashima et al. in 1971, but later by other authors,12,46,51,54,55,82,89 among them Ohihara, Nagashima, and coworkers in 1996, who observed lymphocytes and neutrophils within follicular epithelium and around it72. Prominent infiltrates of eosinophils in company with neutrophils in the epidermis and the dermis have been mentioned in several reports about prurigo pigmentosa.15,23,42–44,46,49,51,54,55,74,77,81,82,89
 
The results of direct immunofluorescence were provided in 21 patients with prurigo pigmentosa, that procedure having been performed for the purpose of excluding dermatitis herpetiformis. The results always were either nonspecific14,25,37 or negative. 6,12,13,17,19–21,23,24,32,33,42,60,76,90
 
Immunhistochemical studies were recorded in seven articles about prurigo pigmentosa,7,38,40,46,51,61,73 but it is difficult to interpret the results of them. Teraki et al. noted similarities to changes in fixed drug eruption, particularly in regard to expression of ICAM-1. Moreover, they told of CD8+ cells at the dermo-epidermal junction7, a finding observed also by Fujita and Arai et al.51, but not by Sakamoto et al., who found T lymphocytes at the dermo-epidermal junction to be CD4+46, and who spotted CD8+ T lymphocytes in early lesions especially.
 
Few lesions of prurigo pigmentosa have been studied by electron microscopy and, on the whole, those findings, too, have been said to be "nonspecific."10,16,17,33,40,53,56 For the most part, they merely confirm what is seen by conventional micoscropy, namely spongiosis, damage to basal cells of the epidermis, and a superficial perivascular infiltrate of lymphocytes. Schepis et al. claimed to have seen signs of acantholysis in basal keratocytes, an increased number of melanocytes at the dermo-epidermal junction, and melanin granules in basal keratocytes.16,17 Other authors observed numerous melanophages in the upper part of the dermis.10,33
 
In short, most of those who studied sections of tissue from biopsy specimens of prurigo pigmentosa by conventional micoscropy recorded only "nonspecific" findings, namely, spongiosis, slight interface changes, a superficial perivascular infiltrate of lymphocytes and melanophages, epidermal hyperplasia, ortho- and parakeratosis, erosions, and crusts. Some, however, took note in early lesions of neutrophils in the upper part of the dermis and in the epidermis.
 
Staining by direct immunofluorescence is nonspecific or negative.