Our Observations

 
We studied sections of tissue from 28 biopsy specimens taken from 15 patients with prurigo pigmentosa at different stages of the disease. Photomicrographs of these sections are shown in Figures 15–23. The findings histopathologically transpire rapidly, just as do the features clinically, an individual lesion lasting less than a week, from beginning to end. The process is extraordinarily dynamic and the changes morphologically, both clinically and histopathologically, are singular. The disease is typified by very different changes at each stage of it, those stages being designated arbitrarily by us as "early", "fully developed", and "late".
 
In an early lesion of prurigo pigmentosa, that is, a smooth-surfaced reddish macule or an urticarial papule, the infiltrate is sparse, perivascular, and interstitial, and consists of neutrophils overwhelmingly, those polymorphs being joined by a rare lymphocyte around a venule of the superficial plexus and by an occasional eosinophil in the interstitium of the upper part of the reticular dermis (Figs. 15 A–D). Even very early in the course, some nuclear "dust" of neutrophils is apparent. Although both plexuses may be involved, the infiltrate clearly is "top heavy". The venules especially, but also the capillaries, are stuffed with neutrophils. In edematous dermal papillae, neutrophils are scattered, some being present even at the tip of them (Figs.16 A–D); they are sprinkled, too, along the dermo-epidermal junction. In foci, degeneration of collagen bundles, evidenced by basophilia, may be observed episodically as a consequence of the effect on them of products of neutrophils. Numerous neutrophils and a few eosinophils soon enter the slightly spongiotic epidermis, where they mostly are distributed diffusely (Figs. 17 A–C), but also in clusters. The latter may be situated in spongiotic vesicles or take the form of abscesses that resemble those of Munro and of Kogoj in psoriasis. The neutrophils tend to be more numerous in the upper part of the viable epidermis, but, at this stage, however, they are unassociated with parakeratosis; the cornified layer is normal (Figs. 18 A–C). An individual necrotic keratocyte is found at times within the epidermis in the vicinity of neutrophils.

View Figure  		Fig. 15A  Prurigo pigmentosa, early lesion. At low magnification, an infiltrate of inflammatory cells is discernable around venules of the superficial plexus, in the intestitium of the upper part of the reticular dermis, and in the papillary dermis.

View Figure  		Fig. 15B  Prurigo pigmentosa, early lesion. At higher magnification, the infiltrate is seen to consist of neutrophils almost exclusively. Some nuclear "dust" of neutrophils is present, too.

View Figure  		Fig. 15C  Prurigo pigmentosa, early lesion. No inflammatory cells have yet entered the epidermis.

View Figure  		Fig. 15D  Prurigo pigmentosa, early lesion. Neutrophils, in company with a rare lymphocyte, are scattered in the interstitium.

View Figure  		Fig. 16A  Prurigo pigmentosa, early lesion. At low magnification, an infiltrate of inflammatory cells is noticable around venules of the superficial plexus, in edematous dermal papillae, and in the interstitium of the upper part of the reticular dermis.

View Figure  		Fig. 16B  Prurigo pigmentosa, early lesion. At higher magnification, the infiltrate in dermal papillae is seen to consist of neutrophils mostly.

View Figure  		Fig. 16C  Prurigo pigmentosa, early lesion. Neutrophils are present both diffusely and in incipient collections, along with a few eosinophils and lymphocytes, in the dermal papillae. Some neutrophils are disposed as solitary units at the dermo-epidermal junction. The cornified layer is normal, that is, basket-woven, an indication of how early in the process this lesion is.

View Figure  		Fig. 16D  Prurigo pigmentosa, early lesion. Neutrophils and a rare eosinophil are distributed in the interstitium of the upper part of the reticular dermis. A smattering of lymphocytes is found in close proximity to venules of the superficial plexus.

View Figure  		Fig. 17A  Prurigo pigmentosa, early lesion. At low magnification, a modately dense infiltrate of inflammatory cells can be seen to be situated around venules of the superficial plexus, in the edematous papillary dermis, in the upper part of the reticular dermis, and in the epidermis.

View Figure  		Fig. 17B  Prurigo pigmentosa, early lesion. At higher magnification, lymphocytes are evident around venules of the superficial plexus, and numerous neutrophils are dispersed in the papillary dermis and throughout the epidermis, at all levels of it. Eosinophils are present, too.

View Figure  		Fig. 17C  Prurigo pigmentosa, early lesion. Spongiosis is apparent in the lower part of the epidermis in company with scattered neutrophils, necrotic keratocytes, neutrophils, and an occasional eosinophil, and lymphocytes are present in the edematous papillary dermis. The cornified layer has a normal basket-woven pattern, a tell-take sign that the changes shown are of recent onset.

View Figure  		Fig. 17D  Prurigo pigmentosa, early lesion. The infiltrate in the interstitium of the upper part of thereticular dermis consists predominantly of neutrophils, whereas around the venules of the superficial plexus lymphocytes predominate.

View Figure  		Fig. 18A  Prurigo pigmentosa, early lesion. At low magnification, an infiltrate of inflammatory cells is noted to be present around venules in the upper part of the reticular dermis, in the papillary dermis, and in the epidermis.

View Figure  		Fig. 18B  Prurigo pigmentosa, early lesion. Neutrophils nearly monopolize in the interstitium and many of them are distributed diffusely in the epidermis, where they form collections within spongiotic vesicles.

View Figure  		Fig. 18C  Prurigo pigmentosa, early lesion. Neutrophils are sprinkled in the edematous papillary dermis and are housed in spongiotic vesicles. Ballooning and incipient necrosis of keratocytes also are visualizable.

View Figure  		Fig. 18D  Prurigo pigmentosa, early lesion. Lymphocytes, eosinophils, and neutrophils are scattered in the interstitium.
 
In a fully developed lesion, that is, a crusted red papule, a smooth-surfaced papulovesicle, or, uncommonly, a vesicle, foci of necrosis are observable in the immediate vicinity of abscesses situated in the upper part of the viable epidermis (Figs. 19 A–D); on occasion the necrosis may be en masse. As the process continues to evolve, nuclear "dust" of neutrophils, eosinophils (which, episodically, may be numerous), and lymphocytes accompany neutrophils, first around venules of the superficial plexus, then in the upper part of the dermis and, at last, in the epidermis. Extravasated erythrocytes are evident, sometimes in formidable numbers, around venules and often in the papillary dermis where edema may be striking (Figs. 20 20 A–D). Lymphocytes appear, in ever-increasing number, around venules of the superficial plexus. When lymphocytes enter the spinous zone of the epidermis, spongiosis may be marked. Sometimes vacuoles seem to form in intercellular spaces. Some keratocytes, especially in the lower part of the epidermis, become ballooned. Necrotic keratocytes disposed as solitary units are seen along the dermo-epidermal junction and clusters of them sometimes are observed in the lower part of the epidermis. In some lesions, eosinophils may outnumber neutrophils in the upper part of the dermis and at the dermo-epidermal junction. A blister may develop within the epidermis as a result of a combination of ballooning and spongiosis, or beneath the epidermis consequent to extensive vacuolar alteration at the dermo-epidermal junction (Figs. 21 A–F). All these changes still may be covered by a cornified layer, whose configuration is basket woven, an evidence for how dynamic the process is. Later, scale-crusts that contain neutrophils and a few lymphocytes appear in foci. Lymphocytes come to predominate, not only around venules, but also in the upper part of the dermis, where they tend to form a patchy lichenoid pattern that obscures the dermo-epidermal junction. Rete ridges are elongated and jagged (Figs. 22 A–). Some neutrophils and nuclear "dust" of neutrophils, as well as variable numbers of eosinophils, still are present in the infiltrate. Mounds of parakeratosis are prominent.

View Figure  		Fig. 19A  Prurigo pigmentosa, fully developed lesion. At low magnification, the infiltrate of inflammatory cells is seen to be superficial perivascular and interstitial, and to be present along the dermo-epidermal junction and within the necrotic epidermis.

View Figure  		Fig. 19B  Prurigo pigmentosa, fully developed lesion. At higher magnification, aggregations of neutrophils are present within the necrotic epidermis, especially the upper part of it. Neutrophils are distributed diffusely in the upper part of the dermis.

View Figure  		Fig. 19C  Prurigo pigmentosa, fully developed lesion. The collections of neutrophils are situated in the upper part of the necrotic epidermis, in the lower half of which there are both spongiosis and ballooning. A few lymphocytes are sprinkled along the dermo-epidermal junction and within the epidermis. Neutrophils and some nuclear "dust" of neutrophils are housed in the papillary dermis. The epidermis is covered still by a normal stratum corneum with its basket-woven configuration, which signals that the course of the process was rapid.

View Figure  		Fig. 19D  Prurigo pigmentosa, fully developed lesion. Lymphocytes, eosinophils, and neutrophils are surround venules of the superficial plexus.

View Figure  		Fig. 20A  Prurigo pigmentosa, fully developed lesion. At low magnification, lymphocytes can be seen to predominate around venules of the superficial plexus. Some inflammatory cells are situated in the interstitium of the reticular dermis and in the markedly edematous papillary dermis. Spongiotic vesicles are present within the slightly hyperplastic epidermis.

View Figure  		Fig. 20B  Prurigo pigmentosa, fully developed lesion. At higher magnification, the perivascular and interstitial infiltrate of lymphocytes mostly, the striking edema in the papillary dermis, and the spongiotic vesicles in a hyperplastic epidermis are seen better.

View Figure  		Fig. 20C  Prurigo pigmentosa, fully developed lesion. Lymphocytes predominate around venules, and lymphocytes and neutrophils are apparent within the spongiotic vesicle.

View Figure  		Fig. 20D  Prurigo pigmentosa, fully developed lesion. Lymphocytes are dominant around venules and eosinophils are preponderant in the interstitium.

View Figure  		Fig. 21A  Prurigo pigmentosa, fully developed lesion. At low magnification, a blister can be recognized to have formed in the upper part of the epidermis, where it then became positioned beneath the cornified layer. An infiltrate of lymphocytes is present around venules of the superficial plexus, in the papillary dermis, along the dermo-epidermal junction, and within the epidermis.

View Figure  		Fig. 21B  Prurigo pigmentosa, fully developed lesion. At higher magnification, on the left hand side, the intraepidermal blister is noted to be associated with necrotic keratocytes that appear red in this section stained by hematoxylin and eosin.

View Figure  		Fig. 21C  Prurigo pigmentosa, fully developed lesion. At still higher magnification, lymphocytes predominate within the infiltrate, the papillary dermis is edematous, and spongiosis is present subtly. There is a collection of neutrophils in the upper part of the epidermis, and there is a large intraepidermal blister.

View Figure  		Fig. 21D  Prurigo pigmentosa, fully developed lesion. At very high magnification, lymphocytes in the edematous papillary dermis, incipient necrotic keratocytes, and the abscess beneath the cornified layer are visualizable better.

View Figure  		Fig. 21E  Prurigo pigmentosa, fully developed lesion. At low magnification, on the right hand side, the infiltrate of lymphocytes is present around venules of the superficial plexus, in the interstitium in the upper part of the dermis, along the dermo-epidermal junction, and within an epidermis that houses necrotic keratocytes and sports an intraepidermal vesicle.

View Figure  		Fig. 21F  Prurigo pigmentosa, fully developed lesion. At higher magnification, spongiosis, ballooning, and necrotic keratocytes are found in conjunction with lymphocytes that also are notable at the dermo-epidermal junction.

View Figure  		Fig. 21G  Prurigo pigmentosa, fully developed lesion. Lymphocytes, eosinophils, and extravasated erythrocytes are numerous in the papillary dermis.

View Figure  		Fig. 22A  Prurigo pigmentosa, fully developed lesion. At low magnification, lymphocytes can be observed around venules of the superficial plexus, in patchy band-like fashion in the upper part of the dermis, along the dermo-epidermal junction, and in the lower part of the epidermis, which has a jagged outline.

View Figure  		Fig. 22B  Prurigo pigmentosa, fully developed lesion. At higher magnification, a patchy lichenoid infiltrate of lymphocytes is seen to be accompanied by edema, and the epidermis, with its jagged outline, can be told to be incipiently necrotic by virtue of the eosinophilic cast of the keratocytes.

View Figure  		Fig. 22C  Prurigo pigmentosa, fully developed lesion. Lymphocytes in the edematous papillary dermis, the incipiently necrotic epidermis, and parakeratosis, are seen to better advantage.

View Figure  		Fig. 22D  Prurigo pigmentosa, fully developed lesion. Lymphocytes nearly monopolize in the immediate vicinity of venules of the superficial plexus.
 
In a late lesion, that is, a pigmented macule, the sparse perivascular infiltrate consists of lymphocytes mainly and hardly of any neutrophils or eosinophils (Figs. 23 A–C). The epidermis may house a tad of spongiosis and, in foci, display parakeratosis. At the end of the process, melanophages are situated in the papillary dermis in numbers that range from few to many. The epidermis itself is hyperpigmented and the density of melanin in it ranges from slight to marked. Alternatively, at the very end, a subtly pigmented macule may exhibit hyperpigmentation of the epidermis but no melanophages in the papillary dermis.

View Figure  		Fig. 23A  Prurigo pigmentosa, late lesion. At scanning magnification, a sparse infiltrate of mononuclear cells is found around venules of the superficial plexus. The epidermis is ever so slightly hyperplastic.

View Figure  		Fig. 23B  Prurigo pigmentosa, late lesion. At higher magnification, the infiltrate can be seen to be made up of lymphocytes and melanophages.

View Figure  		Fig. 23C  Prurigo pigmentosa, late lesion. Melanophages can be seen well.

View Figure  		Fig. 23D  Prurigo pigmentosa, late lesion. Melanophages, situated in close proximity to venules, predominate.
 
In sum, prurigo pigmentosa begins with a sparse superficial perivascular infiltrate made up almost entirely of neutrophils and, shortly thereafter, neutrophils are found scattered in the interstitium of the upper half of the reticular dermis, in an edematous papillary dermis, along the dermo-epidermal junction, and in the lowermost part of the slightly spongiotic epidermis. Those neutrophils then "sweep" through the epidermis, where they are distributed diffusely, eventually coming to be positioned mostly in the upper part of it, mainly as solitary units but also in clusters of poorly formed abscesses and in spongiotic vesicles. Necrotic keratocytes appear as solitary units and in clusters, or even as confluence en masse, in the immediate vicinity of neutrophils. Eosinophils, which occasionally may be numerous, and lymphocytes, which may assume a patchy lichenoid pattern, come to predominate over neutrophils both in the dermis and the epidermis. Spongiosis and ballooning may lead to intraepidermal vesiculation, and extensive vacuolar alteration to subepidermal clefts and subepidermal vesiculation. Scale-crusts house neutrophils and few lymphocytes. Later, when lymphocytes predominate, the epidermis becomes slightly hyperplastic and parakeratotic. Eventually, melanophages appear in the papillary dermis and the epidermis itself becomes hyperpigmented.