Clinical Presentation of Mucosal Acute and Chronic Graft-Versus-Host Disease



Fig. 4.1
Ocular graft-versus-host disease. Ocular GVHD can affect almost every structure of the eye. Distinctive characteristics of chronic ocular GVHD include keratoconjunctivitis sicca, confluent areas of punctate keratopathy, and cicatricial conjunctivitis. (a) Acute ocular GVHD can present with pseudomembranous conjunctivitis and sloughing of the cornea, which can be visualized using fluorescein dye staining or slit lamp examination. (b) Complete loss of eyelashes may also be seen in the setting of acute ocular GVHD. (c) In chronic ocular GVHD, punctate keratopathy involving the cornea and conjunctiva can be seen in the setting of keratoconjunctivitis sicca, or dry eye syndrome, and can be visualized with the aid of dyes including fluorescein, lissamine green (as shown), and rose Bengal. (d) Blepharitis, or inflammation of the eyelids, may also be observed and can lead to trichiasis—ingrowth or misdirection of eyelashes, which can result in corneal abrasion. (e) Chronic inflammation of the ocular mucosa can lead to conjunctival fibrosis, which can be visualized with eyelid eversion (Photos courtesy of Manuel B. Datiles III, MD)



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Fig. 4.2
Diagnostic and distinctive features of oral GVHD. Chronic GVHD may be clinically diagnosed by the presence of lichen planus–like hyperkeratosis on the oral mucosa in a patient who has undergone stem cell transplantation. (a) Chronic GVHD may present as white reticulate, hyperkeratotic plaques on the buccal mucosa. (b) Erythema, hyperkeratotic plaques, and pseudomembranous ulceration may be observed in chronic GVHD. Acute GVHD may have a similar ulcerated presentation with mild erythema and without hyperkeratotic plaques. (c) Mucocutaneous candidiasis, presenting here as white plaques on the posterior soft palate and anterior pillar of fauces (arrows) and yellow-coated tongue, can mimic acute or chronic GVHD but is generally accompanied by a burning sensation relieved with topical and systemic antifungal therapy


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Fig. 4.3
Oral ulcerations in post-transplant patients. Ulcerations may occur at any site on the oral mucosa, including the roof of the mouth, buccal mucosa, tongue, gingiva, vestibules, and lips. Establishing a clear diagnosis is critical for successful treatment. Ulcers may result from GVHD, viral infection, systemic medications or other causes. (a) Acute GVHD may present as mucositis involving any site on the oral mucosa (Photo courtesy of Robert Range, DDS). (b, c) Pseudomembranous ulcerations in chronic GVHD occur in many forms, and may eventually lose their pseudomembranous covering. Common sites include the base of the ventral tongue and the buccal mucosa. (d) Chronic GVHD may present on the cutaneous lip as wide, irregularly shaped ulcers in the setting of white lacy lesions, chapping, or generalized superficial hyperkeratosis of the cutaneous lip. (e) Ulcerations on the cutaneous lip may also be caused by viruses, including herpes simplex virus (HSV). HSV presents as clustered vesicles that, when unroofed, leave punched-out ulcerations. (f) Sirolimus, and less frequently other mTOR inhibitors, may induce isolated painful oral ulcerations, mucositis, or stomatitis. These findings typically occur in the setting of supratherapeutic serum drug levels and resolve with adjustment of drug dose. Palliative care may be required to help reduce oral pain until resolution of the ulcers


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Fig. 4.4
Palatal changes in oral chronic GVHD. Alterations in the palatal mucosa may be seen in chronic GVHD. (a) Palatal hyperkeratosis, erythema, and ulceration may be present on the hard palate and soft palate in chronic GVHD. (b) The presence of mucoceles is a distinctive, but not diagnostic, sign of oral chronic GVHD. Mucoceles occur when the ductal openings of the minor salivary glands are blocked, either with foreign material or because of lymphocytic infiltrate in the underlying skin or salivary glands. These are most commonly seen on the lower labial mucosa and at the junction between the hard and soft palate. Though typically painless, mucoceles may be bothersome and slow to resolve. (c) Milder changes involving the palate, such as a mottled red and white discoloration, may also be seen in chronic GVHD


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Fig. 4.5
Tongue changes in post-transplant patients. The tongue is a sensitive indicator of changes in the post-transplant period. In the setting of long-standing xerostomia or prolonged oral chronic GVHD, the tongue may lose its filiform and fungiform papillae, resulting in smooth appearance of the dorsal tongue. (a) When xerostomia is induced by chronic GVHD, associated white hyperkeratotic plaques may also be seen on the dorsal surface. (b) Hyperkeratotic plaques on the dorsal tongue may also be patchy and intermixed with patches of atrophy and erythema. (c) Chronic GVHD may induce isolated or multiple tufted, hyperkeratotic papules and plaques on the dorsal tongue, which require careful monitoring and evaluation with diagnostic biopsy to assess for human papillomavirus (HPV) or secondary malignancy


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Fig. 4.6
Genital GVHD. Chronic GVHD of the genitals may manifest as erythema, white plaques, erosions, fissures, ulcerations, or significant scarring resulting in loss of normal genital anatomy if not diagnosed at an early stage. Symptoms include vaginal dryness, pruritus, dyspareunia, and pain to touch around the introitus, particularly concentrated at the Skene’s and Bartholin’s duct openings. Genital GVHD may occur alone, but typically is associated with involvement of other mucosal sites [1]. (a) Chronic lichen planus-like GVHD of the genital mucosa is characterized by reticulate leukokeratosis (Wickham striae) overlying erythematous patches or erosions and can lead to complete resorption of the labia minora (arrow), clitoral hood agglutination (arrowhead), and narrowing of the vaginal orifice (double arrowhead). The vagina should always be examined for involvement in all forms of GVHD. (b) Erosive GVHD is characterized by painful erosions and ulcerations favoring the modified mucous membranes of the labia minora, perineum, clitoral prepuce, vestibule, and vaginal mucosa. The resulting vaginal stenosis, synechiae, and labial adhesions often require surgical correction to maintain sexual and urinary function and to prevent hematocolpos [2]. (c) Lichen sclerosus–like GVHD is characterized by waxy, hypopigmented plaques (arrow) and loss of genital structures secondary to scarring. Agglutination of the labia minora (arrowhead) and clitoral hood scarring (double arrowhead) may be seen. (d) Male genital GVHD is not well characterized. Reported presentations include appearances resembling lichen planus (arrow) or lichen sclerosus, phimosis, meatal scarring [3], and Peyronie’s disease [4]. Coronal fusion (arrowhead) may also be seen



Table 4.1
Differential diagnosis of ocular graft-versus-host disease by clinical features



























 
Xerophthalmia [5]

Ocular irritation or pain [5, 6]

Conjunctival injection (“Red Eye”) [5]

Cicatricial conjunctivitis [7, 8]

DDx

Drug-induceda

Injury secondary to total body irradiation

Infectionb

Other medical conditionsc

Infectionb

Trauma

Infectionb

Glaucoma

Allergy

Chemical irritant

Corneal abrasion

Subconjunctival hemorrhage

Autoimmune diseases (ocular cicatricial pemphigoid)

Postinfectious conjunctivitis

Ocular rosacea

Atopic keratoconjunctivitis

Useful Tests

Schirmer tear test

Tear film breakup time

Meibomian gland exam

Tear osmolarity measurement

Corneal and/or conjunctival stainingd

Slit lamp examinatione

Corneal and/or conjunctival stainingd

Conjunctival or corneal sampling for microbiological evaluation

Slit lamp examinatione

Measurement of intraocular pressure

Corneal and/or conjunctival stainingd

Conjunctival or corneal sampling for microbiological evaluation

Slit lamp examinatione

Eversion of upper and lower lids

Conjunctival or corneal sampling for microbiological evaluation

Conjunctival biopsy ± direct immunofluorescence


DDx differential diagnosis

aMain culprits: antihistamines, beta-blockers, anticholinergics, thiazide diuretics, selective serotonin reuptake inhibitors [9]

bBacterial (Streptococcus, Staphylococcus), viral (adenovirus, herpes simplex virus, cytomegalovirus), fungal (Fusarium, Aspergillus)

cDiabetes, thyroid disorder, vitamin A deficiency, environmental allergies

dWith fluorescein (conjunctival and corneal staining), rose Bengal (conjunctival staining), and/or lissamine green (conjunctival staining), depending on availability and provider preference [10]

eTo examine structures in the anterior eye



Table 4.2
Differential diagnosis of oral graft-versus-host disease by clinical features



























 
Xerostomia

Oral erosions and ulcerations

Mucosal erythema

White patches and plaques

DDx

Drug-induced hyposalivationa

Dehydration

Injury secondary to total body irradiation

Drug-inducedb

Viral infectionc

Gingivitis

Erythematous candidiasis

Irritant or allergic contact mucositis

Wipes away with gauze

Candidiasis/thrush

Pseudomembrane

Fixed

HPV-reactive hyperkeratotic plaque

Leukoplakia

Secondary malignancy (SCC)

Useful tests

Increase patient liquid intake

Review medication list for anticholinergic agents

Palpate major salivary glands to observe saliva expression

Minor labial salivary gland biopsy to assess for histopathologic features of GVHD

Consider trial of cholinergic agonist drug

Assess plasma levels of offending drugb

Viral direct fluorescent antibody, PCR and/or culture

Incisional mucosal biopsy of affected, intact tissue adjacent to defect

Assess for local irritating factors (heavy dental calculus, poor oral hygiene)

KOH preparation and fungal culture for Candida

Incisional mucosal biopsy

KOH preparation and fungal culture for Candida

Incisional mucosal biopsy


DDx differential diagnosis, GVHD graft-versus-host disease, HPV human papillomavirus, KOH potassium hydroxide, PCR polymerase chain reaction, SCC squamous cell carcinoma

aMain culprits: antidepressants, antihistamines, anxiolytics, decongestants, diuretics, muscle relaxants, and agents for neuropathic pain

bmTOR inhibitor

cHerpes simplex, herpes zoster, coxsackie, cytomegalovirus, Epstein-Barr virus



Table 4.3
Differential diagnosis of genital graft-versus-host disease by clinical features



























 
Vulvovaginal dryness [11]

Vulvovaginal erosions and ulcerations [12, 13]

Mucosal erythema [13]

White patches and plaques [13]

Vulvar pain and/or dyspareunia [14]

Vaginal discharge [1517]

DDx

Estrogen deficiency

Drug- induceda

Viral infectionb

Secondary malignancy

Candidiasis

Bacterial infection

Sexually transmitted infections (STI)c

Drug reactiond

Estrogen deficiency

Erythematous candidiasis

Bacterial infection

Irritant or allergic contact dermatitis

Vulvar intraepithelial neoplasia (VIN)

Plasma cell mucositis

Lichen planuse

Lichen sclerosuse

Lichen simplex chronicus

Vitiligo

Postinflammatory pigment alteration

Candidiasis

Condyloma

VIN/squamous cell carcinoma

Estrogen deficiency

Vulvodyniae

Candidiasis

Bacterial infectionf

Trichomoniasis

Atrophic vaginitis

Vaginal intraepithelial neoplasia

Vaginal condyloma

Cervicitisg

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Sep 3, 2017 | Posted by in Dermatology | Comments Off on Clinical Presentation of Mucosal Acute and Chronic Graft-Versus-Host Disease

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