During the active stage of prurigo pigmentosa, the main differential diagnosis is dermatitis herpetiformis. Other diseases which at that stage must be included in the differential diagnosis are linear IgA dermatosis and acute lupus erythematosus. When, in contrast, the condition is quiescent and typified by pigmentation in reticular pattern, the differential diagnosis consists of confluent and reticulated papillomatosis of Gougerot and Carteaud on one hand and macular amyloidosis on the other. Similarities and differences clinically between dermatitis herpetiformis and prurigo pigmentosa are summarized in Table 1. The major criteria for distinguishing pertinent diseases in the differential diagnosis of prurigo pigmentosa follow.

The distribution of lesions and the morphologic attributes of lesions may be very similar in dermatitis herpetiformis and prurigo pigmentosa. Papules in both diseases are red and exceedingly pruritic, that symptom inducing, invariably and inevitably, animated scratching that results in complications such as erosions, ulcerations, and crusts. Red urticarial papules in dermatitis herpetiformis, like those of prurigo pigmentosa, are distributed symmetrically. The shoulders and sacral region are favorite sites in both conditions. In contrast to prurigo pigmentosa, however, dermatitis herpetiformis often has a predilection for the buttocks and extensor surfaces of the extremities, as well as for the scalp. Lesions in dermatitis herpetiformis are grouped (herpetiform) but tend to remain discrete, whereas in prurigo pigmentosa the grouping is not truly herpetiform and the lesions are much more given to confluence, thereby resulting in a netlike pattern. Vesicles are common in dermatitis herpetiformis, but they are rare in prurigo pigmentosa. Unlike the situation in dermatitis herpetiformis, papules in prurigo pigmentosa tend to be distributed in the shape of a wedge that extends from the upper part of the back to the lower part of it, and sometimes those papules assume arcuate and linear shapes. Scales are common in prurigo pigmentosa, but not in dermatitis herpetiformis. Prurigo pigmentosa resolves with pigmentation in characteristic reticular pattern, whereas pigmentation in dermatitis herpetiformis occurs in herpetiform pattern.

No association with glutensensitive enteropathy has been recorded ever in prurigo pigmentosa, unlike the situation in dermatitis herpetiformis, where such an association is common.

Linear IgA dermatosis shares some clinical features with dermatitis herpetiformis. In contrast to prurigo pigmentosa, however, linear IgA dermatosis often involves the scalp and the extensor surface of the limbs. Involvement of mucosae is common in linear IgA dermatosis, but never has been recorded in prurigo pigmentosa. Linear IgA dermatosis and prurigo pigmentosa can be differentiated from one another, too, by the presence of blisters in the former but hardly ever in the latter. In linear IgA dermatosis, lesions often are clustered in cockadelike fashion, whereas that is not the case for prurigo pigmentosa. Postinflammatory hyperpigmentation may occur in linear IgA dermatosis, just as it may in dermatitis herpetiformis, but not in a reticular pattern so typical of prurigo pigmentosa.

Acute lupus erythematosus sometimes presents itself in a manner similar to that of prurigo pigmentosa with an eruption of red macules, papules, and plaques on the neck and chest, usually in photodistribution. A "butterfly blush" typical of acute lupus erythematosus has never been mentioned in a report of prurigo pigmentosa. Lesions in lupus erythematosus often are subtle patches and plaques, whereas those in prurigo pigmentosa are small papules. Bullous lupus erythematosus is characterized by large, as well as small, blisters, whereas, for practical purposes, frank blisters hardly ever occur in prurigo pigmentosa and when they do they are tiny vesicles. In contrast to lesions of prurigo pigmentosa, those in acute lupus erythematosus are not pruritic, but at times are associated with paraesthesia and a sensation of "burning". Postinflammatory hyperpigmentation may be seen in patients with acute lupus erythematosus, but in patchy, rather than reticular, pattern.

In confluent and reticulated papillomatosis of Gougerot-Carteaud, which seems to be a variant of acanthosis nigricans, lesions are distributed symmetrically and with predilection for the sternal and inframammary regions, sites that also may be involved in prurigo pigmentosa. The papillomatosis consists of gray or brown, smooth-surfaced papules that may become confluent to form a reticular pattern akin to that of prurigo pigmentosa. The preferred site for the confluent and reticulated papillomatosis of Gougerot-Carteaud is the anterior trunk. The distribution of lesions in a patient with prurigo pigmentosa is the trunk, particularly the center of it, shoulders, extremities, and, episodically, forehead.

Macular amyloidosis may present itself in a fashion like that of prurigo pigmentosa, that is, pigmentation distributed symmetrically in reticular pattern on the upper part of the back, but there is no tendency for a sweep in wedge shape along the midline, and the lesions themselves are neither urticarial nor scaly. Macular amyloidosis in contrast to prurigo pigmentosa, is not an inflammatory disease.