Dr. Knisley was from and Dr. Mackey is from Advanced Desert Dermatology/Midwestern University, Glendale, Arizona. Dr. Knisley currently is from Florida Dermatology & Skin Cancer Centers, Lake Wales. Dr. Petropolis is from the Section of Dermatology, Sierra Vista Community Health Center, Arizona.
The authors report no conflict of interest.
Correspondence: Raymond R. Knisley, DO, 421 Linden Ln, Lake Wales, FL 33859 (rayknisley@yahoo.com).
A 71-year-old woman presented with pink to violaceous, flat-topped, polygonal papules on the volar wrists, extensor elbows, and bilateral lower legs of 3 years’ duration. She also had erythematous, violaceous, infiltrated plaques with microvesiculation on the bilateral thighs of several months’ duration. She reported pruritus, burning, and discomfort. Her medical history included type 2 diabetes mellitus, hypertension, and asthma with no history of skin rashes. Workup revealed lichen planus pemphigoides (LPP), a rare papulosquamous and vesiculobullous dermatosis that shares features of both lichen planus (LP) and bullous pemphigoid (BP). Despite multiple traditional therapies, her disease continued to progress, further developing mucosal disease. After a review of the literature on LP, BP, and LPP, it was noted that tumor necrosis factor α (TNF-α), along with other cytokines, plays a pivotal role in all 3 diseases. After several conventional systemic therapies failed, we treated our patient with ustekinumab with favorable results.
Lichen planus pemphigoides (LPP) is a rare autoimmune subepidermal blistering disease with few cases reported in the literature.
Because tumor necrosis factor 11α (TNF-11α) and other inflammatory cytokines are involved in the pathogenesis of bullous pemphigoid and lichen planus, it is feasible that they also may be involved in the pathogenesis of LPP.
Ustekinumab may be used to treat LPP as a potential corticosteroid-sparing agent because it indirectly blocks TNF-α, as well as other proinflammatory cytokines such as IFN-γ, IL-17, and IL-22.
References
Case Report
A 71-year-old woman presented with pink to violaceous, flat-topped, polygonal papules consistent with lichen planus (LP) on the volar wrists, extensor elbows, and bilateral lower legs of 3 years’ duration. She also had erythematous, violaceous, infiltrated plaques with microvesiculation on the bilateral thighs of several months’ duration (Figure 1). She reported pruritus, burning, and discomfort. Her medical history included type 2 diabetes mellitus, hypertension, and asthma with no history of skin rashes. A complete physical examination was performed. Age-appropriate screening for malignancy was negative. Hepatitis B and C antibody serologies were negative. Her medications at the time included risedronate and atenolol, which she had been taking for several years.
Figure 1. Lichen planus pemphigoides presentation with erythematous, violaceous, infiltrated plaques with microvesiculation on the thigh.
Punch biopsies from perilesional skin were submitted for hematoxylin and eosin staining and direct immunofluorescence (DIF). Histopathology showed a subepidermal blistering disease with tissue eosinophilia consistent with lichen planus pemphigoides (LPP)(Figure 2); direct immunofluorescence was positive for IgG, C3, and type IV collagen at the dermoepidermal junction. Serum BP180 was positive at 51 U/mL (reference range, <14 U/mL) and BP230 was negative. She was then started on tetracycline (500 mg twice daily), nicotinamide (500 mg twice daily), prednisone (5 mg daily), and dapsone (100 mg daily).
After 3 months without improvement, tetracycline and nicotinamide were discontinued, prednisone was increased to 10 mg daily, and dapsone was continued. A repeat biopsy was taken from a new area of involvement on the left lower leg, which revealed a psoriasiform dermatitis with interface changes. The DIF was positive for IgG and C3 along the basement membrane. A serum indirect immunofluorescence for BP180 also was positive.
Figure 2. Histopathology revealed a brisk inflammatory infiltrate with a subepidermal split (A)(H&E, original magnification ×4) with multiple eosinophils (B)(H&E, original magnification ×20). A perivascular infiltrate was present with marked eosinophils (C)(H&E, original magnification ×40).
The patient developed mild hemolytic anemia on dapsone; the medication was eventually discontinued. Subsequent treatments included adequate trials of azathioprine, mycophenolate mofetil, and hydroxychloroquine. Azathioprine (150 mg daily) and hydroxychloroquine (400 mg daily) treatment failed. She initially improved on mycophenolate mofetil (500 mg in the morning and 1000 mg in the evening) with flattening of the papules on the arms and legs and decreased erythema. However, mycophenolate mofetil eventually lost its efficacy and was discontinued.
Because several medications failed (ie, tetracycline, nicotinamide, prednisone, dapsone, azathioprine, mycophenolate mofetil, hydroxychloroquine), she was started on ustekinumab (45 mg) initial loading dose by subcutaneous injection (patient’s weight, 63 kg). At 4 weeks, the patient was given the second subcutaneous injection of ustekinumab (45 mg). She experienced marked improvement with no new lesions. The prior lesions also had decreased in size and were only slightly pink. The prednisone dose was tapered to 5 mg daily.
She had near-complete resolution of the skin lesions 12 weeks after the second dose of ustekinumab. Since then, she has had some recrudescence of the papulosquamous lesions but no vesicles or bullae. With the exception of occasional scattered pink papules on the forearms, her condition greatly improved on ustekinumab. She is no longer taking any of the other medications with the exception of prednisone (down to 1 mg daily) with a plan to gradually taper completely off of it.
