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Year : 2013  |  Volume : 58  |  Issue : 5  |  Page : 410
Spongiotic intra-epidermal blister: A pitfall in the histopathologic diagnosis of bullous pemphigoid

Department of Dermatology, P. D. Hinduja Hospital and Medical Research Centre, Mahim, Mumbai, Maharashtra, India

Date of Web Publication30-Aug-2013

Correspondence Address:
Rajiv Joshi
Department of Dermatology, P. D. Hinduja Hospital and Medical Research Centre, Mahim, Mumbai, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-5154.117355

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How to cite this article:
Joshi R. Spongiotic intra-epidermal blister: A pitfall in the histopathologic diagnosis of bullous pemphigoid. Indian J Dermatol 2013;58:410

How to cite this URL:
Joshi R. Spongiotic intra-epidermal blister: A pitfall in the histopathologic diagnosis of bullous pemphigoid. Indian J Dermatol [serial online] 2013 [cited 2021 Sep 24];58:410. Available from:


Eosinophils are a conspicuous and major component of the inflammatory cell infiltrate in the bullae and in the dermis in bullous pemphigoid and pemphigoid gestationis. They are also found in certain arthropod reactions, particularly in sensitized individuals, and in some bullous drug reactions. [1]

Histopathological diagnosis of bullous pemphigoid is made in the presence of a unilocular sub-epidermal blister with eosinophils in the dermis. [1] Eosinophilic spongiosis has been described as a finding in early urticarial plaques of pemphigoid when the biopsy is taken from an erythematous edematous plaque. [1]

Literature however, does not mention findings of intra-epidermal spongiotic blisters in biopsies of vesicles of pemphigoid.

DIF findings in pemphigoid are linear band like deposits of IgG and C3 at the dermo-epidermal junction which, usually localize to the roof of a blister obtained by salt split technique. [2]

A skin biopsy taken from a vesicle on the forearm of a 61-year-old man was received for reporting. It revealed a large multilocular intra-epidermal blister filled with numerous eosinophils [Figure 1]. There was mild spongiosis adjacent to the blister with few eosinophils in the spongiotic spinous zone below the blister [Figure 2]. The upper dermis had numerous eosinophils scattered within it with mild dermal edema [Figure 3]. No sub-epidermal blister was seen on deeper sections taken through the block. No features of regeneration of epidermis were seen to suggest artifactual intra-epidermal location of the blister due to regeneration of the epidermis.
Figure 1: Multilocular, intraepidermal blister. (H and E, ×40)

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Figure 2: Blister cavity containing numerous eosinophils with mild spongiosis of adjacent epidermis. (H and E, ×400)

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Figure 3: Eosinophils in the blister cavity, in the epidermis beneath the blister and in the underlying upper dermis. (H and E, ×400)

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A diagnosis of intra-epidermal spongiotic blister with numerous epidermal and dermal eosinophils was rendered with insect bite as a possible diagnosis.

On enquiry with the referring clinician the following history was elicited: The patient had presented with pruritic vesicular eruptions mostly over both upper and lower limbs since seven months without any mucosal involvement. There were numerous small tense vesicles (0.5-1 cm in size) with negative bulla spread sign and Nikolsky sign was not elicitable in the adjacent clinically normal skin. The clinical differential diagnosis was dermatitis herpetiformis, bullous lichen planus, linear IgA dermatosis and vesicular pemphigoid. No relevant medical history was present and there was no history of drug ingestion prior to onset of the disease.

Apart from the biopsy for routine H and E sections, a biopsy from peri-lesional skin had also been submitted for DIF studies.

Direct immunofluorescence showed linear deposits of IgG and C3 at the dermo-epidermal junction with negative IgA. These findings were consistent with pemphigoid and ruled out dermatitis herpetiformis and linear IgA dermatosis. Because salt split technique was not used the differential diagnosis was epidermolysis bullosa acquisita which also shows linear IgG deposits that localize to the base of a split in the epidermis.

Based on the clinical suspicion, numerous eosinophils in the epidermal and dermal infiltrate and DIF findings a final diagnosis of bullous (vesicular) pemphigoid was made.

This case highlights a possible pitfall in the histopathological diagnosis of bullous pemphigoid.

While eosinophilic spongiosis, i.e., mild spongiosis with several eosinophils in the epidermis may be seen in biopsies taken from non-bullous, erythematous, edematous plaques, intra-epidermal spongiotic blisters without sub-epidermal blister has not earlier been reported in biopsies of vesicular or bullous lesions of pemphigoid. This histopathological finding may lead to an erroneous diagnosis of spongiotic dermatitis or insect bite reactions if additional supportive tests like DIF or ELISA for bullous pemphigoid antigens are not available.

In our patient, the correct diagnosis was possible only because DIF was also done in addition to the routine formalin fixed H and E sections.

This case is presented to draw attention of histopathologists and clinicians to the rare possibility of intra-epidermal spongiotic blisters in bullous pemphigoid.

When faced with a case wherein the clinical picture is suggestive of pemphigoid but histopathology shows intra-epidermal spongiotic vesicles with eosinophils, other diagnostic tests, namely, direct immunofluorescence studies or ELISA tests to detect BP antigens 1 and 2 should be asked for before ruling out the diagnosis of bullous pemphigoid.

   References Top

1.Weedon D. Vesiculobullous reaction pattern. In: Weedon D, editor. Skin Pathology. 2 nd ed. London: Churchil Livingstone; 2002. p. 153-5.  Back to cited text no. 1
2.Ahmed AR, Maize JC, Provost TT. Bullous pemphigoid. Clinical and immunologic follow-up after successful therapy. Arch Dermatol 1977;113:1043-6.  Back to cited text no. 2


  [Figure 1], [Figure 2], [Figure 3]


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