At an early stage of the disease, the differential diagnosis of prurigo pigmentosa consists only of urticaria and leukocytoclastic vasculitis early in the course of it. Later in the process, the differential diagnosis must include dermatitis herpetiformis, linear IgA dermatosis, acute lupus erythematosus, eruptive psoriasis, and a pustular expression of dermatophytosis. At the stage when lymphocytes come to predominate and obscure the dermo-epidermal junction, Mucha-Habermann disease has to be taken into account. Table 2 summarizes histopathologic attributes shared by dermatitis herpetiformis and prurigo pigmentosa, and the findings that enable those diseases to be distinguished from one another. Criteria for differentiation of the aforementioned diseases from prurigo pigmentosa follow now.

Both a true hive and an urticarial papule of prurigo pigmentosa are characterized at an early stage by a sparse perivascular and interstitial infiltrate that consists mostly of neutrophils. In contrast to the situation in prurigo pigmentosa, however, the papillary dermis and the dermo-epidermal junction of urtica are spared by the infiltrate.

In leukocytoclystic vasculitis, as in prurigo pigmentosa, an early lesion is typified by a perivascular and interstitial infiltrate of neutrophils especially, in company with nuclear "dust" of neutrophils. In leukocytoclastic vasculitis, however, the amount of "dust" is greater by far.

In both dermatitis herpetiformis and prurigo pigmentosa, an early lesion is typified by a superficial perivascular and interstitial infiltrate made up mostly of neutrophils. In contrast to dermatitis herpetiformis, neutrophils in prurigo pigmentosa are present in the epidermis; in variable numbers when sufficient in number, they tend to form abscesses. The products of those neutrophils cause keratocytes to become necrotic, first as solitary units, then in clusters, and, at times, en masse. As a rule, the epidermis is spared in dermatitis herpetiformis. Unlike the situation in prurigo pigmentosa, dermatitis herpetiformis is typified by the presence of neutrophils at the tip of dermal papillae, in subepidermal spaces, and in subepidermal vesicles. Although spongiotic vesicles may occur in the epidermis of prurigo pigmentosa, they do not do that in dermatitis herpetiformis. In a later lesion, eosinophils predominate in the infiltrate of dermatitis herpetiformis, whereas in prurigo pigmentosa the infiltrate, as a rule, harbors relatively few eosinophils. Last, unlike the situation in prurigo pigmentosa, dermal papillae and subepidermal clefts at the side of a vesicle house of dermatitis herpetiforms neutrophils, nuclear "dust" of neutrophils and band forms. That is not the case in prurigo pigmentosa. Deposits of IgA in dermal papillae are characteristeristic of dermatitis herpetiformis, but no such deposits appear in prurigo pigmentosa. For that reason, staining by direct immunofluorescence is helpful in differentiation of the two diseases.

Linear IgA dermatosis displays histopathologic findings indistinguishable from those of dermatitis herpetiformis. The criteria just mentioned for differentiation histopathologically of dermatitis herpetiformis from prurigo pigmentosa are applicable equally to linear IgA dermatosis. Dermatitis herpetiformis and linear IgA dermatosis differ from one another, not only clinically, but in regard to the results of studies that employ methods of immunofluorescence. Direct immunofluorescence reveals deposits of IgA in dermal papillae of dermatitis herpetiformis, whereas granular deposits of IgA in linear array are present at the basement membrane zone of linear IgA dermatosis, No such findings by immunofluorescence are observed in prurigo pigmentosa.

Acute lupus erythematosus is marked by neutrophils in the upper part of the dermis, along the dermo-epidermal junction, and in the lower part of the epidermis, findings that are somewhat similar to those in prurigo pigmentosa. In prurigo pigmentosa, however, neutrophils are not confined to the lower part of the epidermis; intraepidermal abscesses form often in the middle and upper part of the viable epidermis. Neither spongiosis nor intraepidermal vesiculation occurs in acute lupus erythematosus, but both spongiosis and spongiotic vesicles may be discernible readily in prurigo pigmentosa. Mucin sometimes may be increased in amount in the reticular dermis of lesions of acute lupus erythematosus, but not in that of prurigo pigmentosa. Direct immunofluorescence may reveal deposits of immunoglobulins and complement factors at the dermo-epidermal junction in a lesion of acute lupus erythematosus, but not in prurigo pigmentosa.

Eruptive (guttate) psoriasis exhibits neutrophils at all levels of the epidermis, as is the case, too, for prurigo pigmentosa at an early stage of the process. In contrast to prurigo pigmentosa, however, lesions of eruptive psoriasis display discrete collections of neutrophils in the spinous zone (Munro's microabscesses) and/or in poorly circumscribed collections (spongiform pustules of Kogoj) there and in the granular zone. In guttate psoriasis, neutrophils also may be found at the summit of mounds of parakeratosis that are staggered in the cornified layer; that is not the case for prurigo pigmentosa.

The findings in a pustular expression of dermatophytosis may be just like those in eruptive psoriasis, the only difference between them being hyphae that reside in the cornified layer of a lesion of the infection by a superficial fungus.

In Mucha-Habermann disease, as in a fully developed lesion of prurigo pigmentosa, a patchy lichenoid infiltrate of lymphocytes often obscures the dermo-epidermal junction and lymphocytes are present in the epidermis in company with individual necrotic keratocytes or clusters of them, ballooning, and spongiosis. The infiltrate in the dermis of Mucha-Habermann disease, unlike the situation in prurigo pigmentosa, tends to be wedge-shaped, both deep as well as superficial, and made up entirely of lymphocytes.