Pemphigus vulgaris with nail involvement presenting with vegetating and verrucous lesions
Published Web Locationhttps://doi.org/10.5070/D389j8h509
Pemphigus vulgaris with nail involvement presenting with vegetating and verrucous lesions
Dermatology Department, University Hospital, Coimbra.
R Mascarenhas MD, B Fernandes MD, JP Reis MD, O Tellechea MD PhD, and A Figueiredo MD PhD
Dermatology Online Journal 9 (5): 14
We report the case of a 68-year-old female with longstanding insulin-treated diabetes mellitus, observed for the first time in our department in August 1999 with multiple painful erosive lesions of the oral cavity and many bullous or erosive lesions on the abdominal wall, back, and thigh. She also had vegetating and verrucous lesions, similar to common warts, involving the hands and feet, mainly on the palms, palmar surface of the fingers, and nail folds. Her lesions were present for 1 year. Skin and mucous biopsies showed the characteristic histopathologic findings of pemphigus vulgaris, with an epidermal intercellular IgG deposition on direct immunofluorescence. Histology of a warty lesion of the finger also showed suprabasal acantholysis. After partial improvement with low doses of oral steroids and azathioprine, her disease progressed to involve the oral cavity, trunk, hands, feet, and scalp. Control of her disease required successive treatments of mycophenolate mofetil and cyclophosphamide, as well as corticosteroids. A partial response was obtained with all these treatments. After being controlled by cyclophosphamide that was slowly tapered, she is now well controlled with azathioprine and oral steroids, showing only discrete lesions of the oral mucosa after 1 year of followup. We report this case of pemphigus vulgaris with unusual clinical aspects, namely vegetating and verrucous lesions as well as nail involvement, rarely described in this disease.
Pemphigus vulgaris (PV) is an autoimmune blistering disease, with blisters occurring in the deeper part of the epidermis, above the basal layer.
Clinically it is characterized by flaccid bullae that lead to erosions. These may occur anywhere on the skin, and the involvement of oral mucosa is very common. More rarely, esophagus, rectum, uterus, and vagina may also be affected.
Histopathology reveals suprabasal acantholysis. Direct immunofluorescence (DIF) using the patient's perilesional skin as substrate shows IgG deposition in the intercellular spaces between the keratinocytes. Desmoglein 3, a 130 Kda component of desmosome, is the target antigen in this disease.
Before the corticosteroid era this disease was fatal in 60 percent of patients. Nowadays, with new treatments available (corticosteroids, immunosuppressive drugs, anti-inflammatory drugs and immunomodulatory procedures) mortality is reduced to less than 10 percent, but we now must consider severe adverse side effects of these agents [1, 2].
We report a case of pemphigus vulgaris (PV) with nail involvement and atypical verrucous lesions, rarely described in this entity.
|Figure 1||Figure 2|
|Erosive lesions of the oral mucosa (fig. 1).|
|Bullous and erosive lesion of the thigh (fig. 2).|
|Figure 3||Figure 4|
|Vegetating and verrucous lesions of the left hand, simulating common warts (fig. 3).|
|Warty lesions of the right hand (fig. 4).|
A 68-year-old female was first observed in our department in August 1999 with multiple painful erosive lesions, mainly involving the oral cavity (palate, buccal mucosa, tongue, and lips), and bullous-erosive lesions and crusts involving the skin of thighs, abdominal wall, and back (figs. 1, 2). She also had vegetative verrucous lesions on the periphery of fingernails and digits (palmar surface), some of them clinically similar to common warts (figs. 3, 4), and bullous and vegetating lesions on the skin of both feet (fig. 5), with nail plate destruction of the first toe of left foot and of the third toe of the right foot. Both bullous-erosive and verrucous lesions were present for 1 year. There was no involvement of the axillary or inguinal folds.
She had a longstanding history of insulin-dependent diabetes mellitus. Her mother was also diabetic.
Cutaneous biopsies performed on lower limb and back showed the characteristic histopathologic findings of PV, with prominent suprabasalar acantholysis. DIF, using the patient's perilesional skin as a substrate, showed intercellular deposition of IgG in the epidermis and intercellular deposition of C3 in the epidermis and along the dermal-epidermal junction. Histology of a crusted, verrucous lesion of the finger also showed prominent acantholysis above the basal cell layer, as well as acanthosis and papillomatosis (fig. 6).
She started treatment with oral corticosteroids (methylprednisolone 48 mg per day), azathioprine (50 mg bid) and topical cyclosporine in oral mucosa (100 mg bid). Mucous and cutaneous lesions, including the warty lesions of the fingers and toes, improved considerably, but the use of higher doses of methylprednisolone led to the aggravation of her diabetes, which could not be controlled with the increased doses of subcutaneous insulin, necessitating hospitalization to perform insulin perfusion. For that reason, oral steroids were progressively tapered and finally withdrawn in April 2000.
The patient remained well until October 2000, when mucous and skin lesions recurred, affecting also the face and scalp. A partial response was obtained with the introduction of oral steroids (methylprednisolone 32 mg per day), alone or in association with azathioprine (50 mg bid) or mycophenolate mofetil (2 g daily). However this partial response was followed closely by relapse even under therapy. Azathioprine had to be withdrawn when she developed liver toxicity.
In November she started treatment with cyclophosphamide (50 mg daily and later 100 mg daily) and methylprednisolone (16 mg daily), showing improvement of the disease, maintaining discrete asymptomatic oral lesions and some verrucous lesions of the hands. After 10 months, her disease progressed again and cyclophosphamide was replaced with azathioprine (50 mg daily) and methylprednisolone (24 mg on alternate days). Lesions improved considerably and after 1 year of followup, she maintains this therapy with no liver toxicity from azathioprine, with control of her diabetes on subcutaneous insulin, and with only discrete lesions of oral mucosa.
This case has an unusual presentation with peculiar clinical aspects, vegetating and verrucous lesions as well as nail involvement. These particular clinical findings showed parallel clinical course and response to therapy as did the more typical skin lesions of PV. Vegetating verrucous lesions had the typical histologic hallmark of PV, suprabasalar acantholysis.
Nail involvement in pemphigus is rare and presents mainly as hemorrhagic paronychia. However, other nail findings have been reported, including paronychia, onychomadesis, onycholysis, subungual hyperkeratosis, Beau lines, trachyonychia, and vegetative lesions over paronychia. Although the presence of pemphigus lesions on the skin of the distal phalanges surrounding the nail is well known, none of the reported nail manifestations of pemphigus have the same warty aspect of our patient [3-13]. Nail changes appearing as the primary manifestation of pemphigus vulgaris, either in the nail bed, nail matrix, or nail fold (as seen in our patient), is a rare and infrequently reported phenomenon. Nail involvement usually occurs when the disease is severe, and, in the majority of cases, nail recovery is complete or almost complete after systemic therapy, as in our patient .
Verrucous and vegetating lesions in pemphigus are usually described in pemphigus vegetans, but they are localized to skin folds and characteristic histological findings include epidermal hyperplasia and eosinophilic abscesses, which were absent in our case .
In pemphigus, the deposition of C3 along the dermal epidermal junction is usually associated with paraneoplastic pemphigus. However, in our patient there were no clinical findings such as erythema-multiforme-like, bullous-pemphigoid-like, or lichen-planus-like cutaneous lesions. Our patient had no apparent lymphoproliferative disorder or other neoplasia, and histology did not show keratinocyte necrosis, vacuolar interface dermatitis, or lichenoid infiltrate. Although our patient had treatment difficulties, common in paraneoplastic pemphigus, in our patient the treatment problems could be ascribed to her very severe diabetes mellitus [1, 14].
Despite not achieving total remission, we tried to obtain the right balance between disease activity and iatrogeny. We report this case because of the unusual presentation of pemphigus vulgaris with nail involvement and vegetating and verrucous lesions.
References1. Borradori L, Saurat JH, Les pemphigus. In Dermatologie et Maladies Sexuellement Transmissibles, ed. Saurat JH, Grosshans E, Laugier P, Lachapelle JM, 3e ed. Masson, Paris, 1999: 265-274.
2. Fellner MJ, Spadin NA, Current therapy of Pemphigus Vulgaris, Mt Sinai J Med. 68: 268-278, 2001.
3. Engineer L, Norton LA, Ahmed R, Nail involvement in pemphigus vulgaris, J Am Acad Dermatol. 43: 529-535, 2000.
4. Baumal A, Robinson MJ, Nail bed involvement in pemphigus vulgaris, Arch Dermatol. 107: 751, 1973.
5. Lauber J, Turk K, Beau's lines and pemphigus vulgaris, Int J Dermatol. 29: 309, 1993.
6. Akiyama C, Sou K, Furuya T, Saitoh A, Yasaka N, Ohtake N, et al, Paronychia: a sighn heralding na exacerbation of pemphigus vulgaris, J Am Acad Dermatol. 29: 494-496, 1993.
7. Berker D, Dalziel K, Dawber RPR, Wojnarowska F, Pemphigus associated with nail dystrophy, BR J Dermatol. 129: 461-464, 1993.
8. Kim BS, Song KI, Youn JI, Chung JH, Paronychia - a manifestation of pemphigus vulgaris, Clin Exp Dermatol. 21: 315-317, 1996.
9. Dhawan SS, Zaias N, Pena J, The nail fold in pemphigus vulgaris, Arch Dermatol. 126: 1374-1375, 1990.
10. Riviera RD, Lamazares Jç, Peralto JLR, Vanaclocha FS, Diez LI, Nail involvement in pemphigus vulgaris, Int J Dermatol. 35: 581-582, 1996.
11. Stone OJ, Mullins JF, Vegetative lesions in pemphigus, Dermatol Int. 5: 137-140, 1966.
12. Parameswara YR, Naik RPC, Onichomadesis associated with pemphigus vulgaris, Arch Dermatol. 117: 759-760, 1981.
13. Fulton RA, Campbell I, Carlyle D, Simpson NB, Nail bed immunoflorescence in pemphigus vulgaris, Acta Derm Venereol. 63: 170-172, 1983.
14. Joly P, Richard C, Gilbert D, Courville P, Chosidow O, Roujeau JC, et al, Sensitivity and specificity of clinical, histologic and immunologic features in the diagnosis of paraneoplastic pemphigus, J Am Acad Dermatol. 43: 619-626, 2000.
© 2003 Dermatology Online Journal