Koebner’s Phenomenon in Pemphigus Vulgaris

Dear Editor, A 27-year-old male presented with an ulcer in the left buccal mucosa and tongue, associated with pain, difficulty in swallowing, and bleeding on brushing. Then, over the next 2 months, he developed numerous clear to pale yellow fluid-filled flaccid vesicles and bullae, initially over his chest and subsequently all over his body, associated with mild burning sensation and these ruptured spontaneously leaving behind raw areas, with little tendency to heal. On examination, hypopyon sign was seen in some of the lesions. Thick adherent yellow to brown-colored crusts with multiple erosions were present over the scalp, face, and trunk [Supplementary Figures 1 and 2]. Direct Nikolsky’s sign was negative, and marginal Nikolsky was positive. Bulla spread sign showed irregular spreading margins. Few areas of post inflammatory hyperpigmentation were seen. Palms, soles, nails, ocular, and genital mucosa were normal. All his blood investigations were within normal limits. Skin biopsy and direct immunofluorescence (DIF) confirmed it as pemphigus vulgaris (PV). The patient was subjected to the Mantoux test for evaluation of tuberculosis before immunosuppressants. On the third day of the Mantoux test, he developed a flaccid bulla over the test site [Figure 1]. Skin biopsy from the lesion showed a suprabasal cleft in the epidermis with acantholytic keratinocytes mixed with neutrophils and lymphocytes. Basal keratinocytes were seen separated from each other giving the row of tombstones appearance [Figure 2a and b]. DIF from the periphery of the lesion showed coarse granular deposits of IgG in the intracellular space, giving a fishnet appearance suggestive of PV [Figure 3]. The patient was managed with oral prednisolone in tapering doses and rituximab infusion as per rheumatoid arthritis (RA) protocol.Supplementary Figure 1: Erosions over the scalp in a patient of pemphigus vulgarisSupplementary Figure 2: Erosions over the tongue and perioral regionFigure 1: Flaccid bulla over the tuberculin test siteFigure 2: (a): Suprabasal cleft in the epidermis with acantholytic keratinocytes mixed with neutrophils and lymphocytes (H&E, 10x). (b): Basal keratinocytes separated from each other giving the row of tombstones appearance (H&E, 40x)Figure 3: DIF showing coarse granular deposits of IgG in the intracellular space giving a fishnet appearance (40x)The Koebner phenomenon (KP), also known as an isomorphic phenomenon, first described by Heinrich Koebner in 1876, is defined as the development of new skin lesions as a result of trauma on previously unaffected skin, and the new lesions are clinically and histologically identical to the patient’s underlying cutaneous condition.[1] It is described in several skin disorders like psoriasis and lichen planus but is limited to very few case reports in PV. It is important to differentiate KP from other reactions. The ‘pseudo-Koebner phenomenon’ describes the spread of an infective agent such as the extension of verruca vulgaris or molluscum contagiosum by injury or scratching. A ‘reverse-Koebner phenomenon’ is the resolution of preexisting skin disease at injury sites. The ‘pathergy reaction’ is a hypersensitivity reaction at sites of minor trauma in neutrophilic disorders like Bechet’s disease. The ‘isotopic response’ is defined as the appearance of a new skin disorder at the site of another, unrelated and already healed skin disease. The “Nikolsky’s sign” is defined as the appearance of erosion immediately after lateral pressure on normal-appearing skin, which shows the disease activity and severity. There will be a lag period in KP between the trauma and the development of blisters, ranging from a few years to as little as 3 days. In our instance, a blister developed after 3 days; thus, it is not a Nikolsky sign. The etiopathogenesis of KP in PV is still not clear. It is proposed to be a complex interaction of genetic, local, and systemic factors that influence healing and immune responses.[2] A few proposed theories are explained below. Trauma or other triggers alter the sulfhydryl groups of pemphigus antigens and modify the cell membrane antigenicity and cause acantholysis.[3] Also, skin breach exposes a minimal quantity of pemphigus antigens, enough to react with circulating antibodies at lower titers that would not induce the disease in the intact skin.[4] Additionally, in genetically susceptible patients, trauma overexpresses epidermal antigens, promotes antigen presentation, and results in the epitope-spreading phenomenon. It is hypothesized that the healing process and scarred tissue may fail to support normal keratinocyte differentiation, changing vascular and connective tissue function and rendering the cells more susceptible to low titers of pemphigus autoantibodies.[5] Proinflammatory mediators such as IL1, TNF, and IL 6 that are released nonspecifically after injuries may be responsible for the initial phase, and nonspecific inflammation that is not severe enough to cause blistering earlier induces the recruitment of antigen-specific B- and T-cells, which in turn initiates the second phase. KP is uncommon in PV and major surgeries, or trauma is the cause according to the available literature. We offer this example to highlight the fact that KP in PV can be induced by even small trauma, like a tuberculin test, to distinguish it from other phenomena and to emphasize the need for preventive measures to avoid trauma and worsening of the illness. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.