Here's a diagnostic and perhaps therapeutic challenge.
This well-nourished, alert, well-oriented 82 yo woman presents with a six month history of an erosive dermatitis of the perirectal and vaginal area. Over the past year she has had pathological fractures of both femurs and a history of herpes zoster (not cofirmed). Remarkably, she has put up with these erosions which are apparently not that painful.
O/E: Sharply marginated clean erosions around rectum and vagina. Similar lesions are found in skin folds (abdominal and under breasts). She has some oral ulcerations under her dentures and crusted lesions on the scalp. No vesicles or bullae seen or noted by other physicians.
Lab: At this time CBC normal. Antibodies for pemphigus and pemphigoid are negative.
Biopsies performed on Feb. 8, 2007 for H&E and DIF.
Who has seen a similar picture?
I am thinking about:
Pemphigus variant
Necrolytic migratory erythema
Acrodermatitis enteropathica
Will order zinc and glucagon levels if pathology is not helpful. Someone may have seen this picture before.
Updated February 16, 2007
Here's a follow-up on this patient...
Path: Shows:
Subepidermal blister with dense superficial and mid perivascular and interstitial mixed inflammatory cell infiltrate including lymphocytes, plasma cells, eosinophils , dermal edema, and papillary dermal fibrosis .
NOTE : These changes are non-diagnostic but suggestive of cicatricial pemphigoid in view of the immunofluorescence findings (see below).
See immunofluorescence results and note. (Photo by Jag Bhawan)
DIRECT IMMUNOFLUORESCENCE RESULTS : Linear "Immunostaining" was observed with IgG, IgA and intermittent with C3 at dermal epidermal junction and with C3 and IgA around blood vessels and appendages. NOTE : These changes are non-diagnostic but consistent with cicatricial pemphigoid.
Putting this together, I suspect this is indeed an unusual variant of cicatricial pemphigoid. I have started her on prednisone 20 mg tid and tacrolimus ointment 0.1% (but insurance plans here do not always cover the ointment). A G6PD was ordered since I will probably use Dapson as well. I expect the management will be difficult.
February 22
Patient seen in f/u. To my surprise, there is early reepithelialization of perineal erosions. Oral erosions still prominent. I've lowered her prednisone to 20 mg bid -- awaiting G6PD results. Perhaps, the tacrolimus is helping. The comments havc been helpful.
I would consider erosive lichen planus David especially as the pemphigus abs are negative.
ReplyDeleteThis was sent in by Robert Rudolph
ReplyDelete1. erosive LP
2. erosive LSA
3. antibody negative PV
4. AE
5. No clue.
I would consider
ReplyDelete1. Oro-vaginal Vulvar Lichen planus
2. Paget's disease
3. Paraneoplastic Pemphigus
This comment has been removed by a blog administrator.
ReplyDeleteI agree with the differential given in the case and agree with the biopsy for H&E and DIF. I believe these will help a lot. In addition to the differential given I would add ulcerative lichen planus and extramammary pagets.
ReplyDeletePlease consider Crohns ds with or without intestinal involvement in the differential diagnoses.The finding of biopsy is very helpful in clear cut diagnosis.Also pemphigus vegetans of Hallopeau is important DD.
ReplyDeleteKhalifa sharquie
Was the pt on any prior drugs that might have triggered a clinically atypical linear IgA bullous dermatosis?
ReplyDeleteStill the picture is not in favour of cicat pemphigoid:
ReplyDelete1-The disease does not involve skin folds
2-Fissurings of skin folds are a characterestic featureof Crohns ds rather than cicat pemphigoid
3-the histology and immunoflourecence are non specific in this case
So please reconsider the daignosis again.
khalifa sharquie
We do not believe that this is Crohn’s disease.
ReplyDeleteThe pattern of immune deposition in this case (linear BMZ deposition of IgG, IgA, and C3) has been reported primarily in 2 disease entities: (1) mucosal membrane pemphigoid (synonomous with cicatricial pemphigoid) and (2) epidermolysis bullosa aquisita (EBA). As described below, the clinical presentation of this patient is consistent with mucosal membrane pemphigoid.
Mucosal Membrane Pemphigoid (synonomous with cicatricial pemphigoid) is considered a “disease phenotype” comprised of a heterogenous group of blistering disorders that share a predilection for the mucosal surfaces. Classical lesions in the oral cavity often involve the gingival (ex, erosive gingivitis), buccal mucosa, and palate (ex, chronic erosions). Alveolar ridges, tongue, and lips are less frequently affected. Adhesions may develop in the area of the uvula and tonsillar fossae as well as between the tongue and the floor of the mouth. After healing, lesions may lead to white, reticulated striations, resembling lichen planus. Ocular CP starts as a non-specific, chronic conjunctivitis, with burning, soreness, foreign-body sensation, or mucus production. Both exacerbations and remissions are typical, with eventual progression to subepithelial conjunctival fibrosis.
While the two most frequently involved sites in patients with the 'CP-phenotype' are the oral (seen in up to 85% of patients) and conjunctival mucosae, the disease may start in, and affect, any mucosal site, including the external genitalia, the anus, the upper aerodigestive tract, and/or esophagus. Involvement of genital and anal mucosae is relatively rare. Early lesions consist of blisters and chronic erosions. In female patients, progressive disease leads to atrophic scarring and narrowing of the introitus. In male patients, adhesions can form between the prepuce and the glans penis. Anal involvement can also lead to scarring and, in severe cases, to stricture formation.
Classic EBA presents as a non-inflammatory mechanobullous disease characterized by the development of acral blisters (usually trauma-prone surfaces, such as the elbows, knees, and dorsa of the hands, feet, and toes) that heal with atrophic scarring, milia, and hyper- or hypopigmentation. When EBA presents like inflammatory bullous pemphigoid, intertriginous involvement is accompanied by more widespread vesicles in the the flexural areas. A “CP-like presentation”, including the Brunsting-Perry pemphigoid phenotype with scarring alopecia, usually involves only the head and neck and so does not fit with this patient. Mucous membrane involvement is variable in EBA, and if present, favors the mouth, larynx, esophagus, and ocular conjunctivae. Interestingly, an overlap exists between patients with Crohn’s disease and EBA (ex.,Journal of Investigative Dermatology (2002) 118, 1059–1064). In this case, the biopsy of the skin lesion did not show granulomas consistent with cutaneous Crohn’s. Thus, one would have to argue that this patient has atypical cutaneous lesions of EBA in the setting of undiagnosed Crohn’s disease.
How about a case of "IgG/IgA periorificial pemphigoid/LABD Overlap".
ReplyDelete1: Pediatr Dermatol. 1994 Jun;11(2):139-44.
Linear IgA bullous dermatosis of childhood with autoantibodies to a 230 kDa
epidermal antigen.
Kanitakis J, Mauduit G, Cozzani E, Badinand P, Faure M, Claudy A.
Department of Dermatology, Hopital Ed. Herriot, Lyon, France.
Linear IgA bullous dermatosis (LABD) is an autoimmune, subepidermal disease
defined on the basis of direct immunofluorescence findings. However, more recent
techniques used to study bullous dermatoses suggest that LABD may be
heterogeneous. A patient with LABD of childhood (chronic benign disease of
childhood, CBDC) was studied by indirect immunofluorescence on salt-split skin
and by Western blot in an attempt to characterize the involved autoantigen. This
young girl's periorificial (mouth, genitalia), erythematovesicular lesions were
diagnosed initially as herpes simplex. Histologic examination revealed
eosinophilic spongiosis, suggesting the diagnosis of an autoimmune blistering
disease. Direct immunofluorescence showed an exclusive linear IgA deposit at the
dermoepidermal junction. Indirect immunofluorescence revealed circulating IgA
autoantibodies that reacted with the epidermal side of salt-split skin; these
reacted by Western blot with a 230 kDa epidermal antigen, as in bullous
pemphigoid. This case, fulfilling the diagnostic clinical and direct
immunofluorescence criteria for LABD/CBDC, seems to represent IgA bullous
pemphigoid. It further underscores the nosologic heterogeneity of LABD, which
probably includes, apart from bullous pemphigoid, epidermolysis bullosa
acquisita and cicatricial pemphigoid.
We believe that the changes seen here do not represent Crohn’s disease.
ReplyDeleteThe pattern of immune deposition in this case (linear BMZ deposition of IgG, IgA, and C3) has been reported primarily in 2 disease entities: (1) mucosal membrane pemphigoid (synonomous with cicatricial pemphigoid) and (2) epidermolysis bullosa aquisita (EBA). As described below, the clinical presentation of this patient is consistent with mucosal membrane pemphigoid.
Mucosal Membrane Pemphigoid (synonomous with cicatricial pemphigoid) is considered a “disease phenotype” comprised of a heterogenous group of blistering disorders that share a predilection for the mucosal surfaces. Classical lesions in the oral cavity often involve the gingival (ex, erosive gingivitis), buccal mucosa, and palate (ex, chronic erosions). Alveolar ridges, tongue, and lips are less frequently affected. Adhesions may develop in the area of the uvula and tonsillar fossae as well as between the tongue and the floor of the mouth. After healing, lesions may lead to white, reticulated striations, resembling lichen planus. Ocular CP starts as a non-specific, chronic conjunctivitis, with burning, soreness, foreign-body sensation, or mucus production. Both exacerbations and remissions are typical, with eventual progression to subepithelial conjunctival fibrosis.
While the two most frequently involved sites in patients with the 'CP-phenotype' are the oral (seen in up to 85% of patients) and conjunctival mucosae, the disease may start in, and affect, any mucosal site, including the external genitalia, the anus, the upper aerodigestive tract, and/or esophagus. Involvement of genital and anal mucosae is relatively rare. Early lesions consist of blisters and chronic erosions. In female patients, progressive disease leads to atrophic scarring and narrowing of the introitus. In male patients, adhesions can form between the prepuce and the glans penis. Anal involvement can also lead to scarring and, in severe cases, to stricture formation.
Classic EBA presents as a non-inflammatory mechanobullous disease characterized by the development of acral blisters (usually trauma-prone surfaces, such as the elbows, knees, and dorsa of the hands, feet, and toes) that heal with atrophic scarring, milia, and hyper- or hypopigmentation. When EBA presents like inflammatory bullous pemphigoid, intertriginous involvement is accompanied by more widespread vesicles in the the flexural areas. A “CP-like presentation”, including the Brunsting-Perry pemphigoid phenotype with scarring alopecia, usually involves only the head and neck and so does not fit with this patient. Mucous membrane involvement is variable in EBA, and if present, favors the mouth, larynx, esophagus, and ocular conjunctivae. Interestingly, an overlap exists between patients with Crohn’s disease and EBA (ex.,Journal of Investigative Dermatology (2002) 118, 1059–1064). In this case, the biopsy of the skin lesion did not show granulomas consistent with cutaneous Crohn’s. Thus, one would have to argue that this patient has atypical cutaneous lesions of EBA in the setting of undiagnosed Crohn’s disease.
Just a note on this erosive case. When I see mucous membranes involved, especially unusual sites like the perianal area depicted here, and skin, I think of Kim Yancey’s disease, so called aniepillagrin or anti laminin 5 type of cicatricial pemphigoid. The importance of this is that there is a high rate of associated cancer. Kim would likely run a test to see if this patient’s antibodies react to laminin.
ReplyDelete