7.2 Chronic GVHD Diagnostic Manifestations, BOS & NIH Global Severity Scoring

1. NIH Diagnostic and Distinctive Manifestations

A diagnostic manifestation can establish chronic GVHD by itself after alternatives are excluded. A distinctive manifestation is suggestive but requires pertinent biopsy, laboratory testing, specialist assessment, radiology, or chronic-GVHD evidence in the same or another organ.

• Skin diagnostic: poikiloderma; lichen-planus-like, lichen-sclerosus-like, morphea-like, or deep sclerotic features. Depigmentation and papulosquamous lesions are distinctive. Erythema, maculopapular rash and pruritus occur in acute and chronic disease and are not diagnostic alone.
• Mouth diagnostic: lichen-planus-like white/lacy changes. Xerostomia, mucoceles, atrophy, ulcers and pseudomembranes are distinctive. Isolated hyperkeratotic plaque/leukoplakia is not diagnostic and needs malignancy evaluation.
• Eyes: dry/gritty/painful eye, cicatricial conjunctivitis, keratoconjunctivitis sicca and punctate keratopathy are distinctive, not standalone diagnostic findings. Ophthalmic examination helps attribution; Schirmer testing is not a universal severity score.
• Esophagus/GI: esophageal web, stricture or upper-third narrowing is diagnostic. Anorexia, nausea, vomiting, diarrhea and weight loss are nonspecific and need evaluation for acute GVHD, infection, drugs and other causes.
• Fascia/joints: fasciitis, groove sign, and stiffness/contracture secondary to sclerosis are diagnostic. Myositis/polymyositis is distinctive and requires confirmation.
• Genital tract: NIH-specified lichen-planus-like features and scarring/stenosis are diagnostic; erosions, fissures and other symptoms need specialist attribution.
• Liver: no standalone diagnostic or distinctive clinical feature; cholestatic or hepatitic tests require evaluation for drugs, viruses, iron, obstruction, SOS and other causes.

Bronchiolitis Obliterans Syndrome

BOS is an obstructive small-airway syndrome. Clinical NIH criteria use FEV1/VC below 0.70 or the fifth percentile, FEV1 below 75% predicted with at least 10% decline over less than two years, and absence of active respiratory infection. Supporting evidence is either another chronic-GVHD manifestation or air trapping/bronchiectasis on expiratory CT, RV over 120% predicted, or RV/TLC above the 90th percentile. If lung is the only involved site without a distinctive manifestation elsewhere, biopsy-proven bronchiolitis obliterans may be required to establish chronic GVHD for the NIH framework. Trend PFTs because early BOS may be asymptomatic.

2. NIH Organ Staging System (0 to 3 Scale)

Every organ system is scored individually on a validated scale from 0 (no involvement) to 3 (severe, functionally incapacitating involvement):

3. Calculation of NIH Global Severity Score & Prognostic Utility

The NIH Global Severity Score combines the individual 0–3 organ scores into mild, moderate, or severe categories that standardize communication and inform risk and treatment planning; the category alone does not dictate one therapy:

                    NIH GLOBAL SEVERITY SCORE ALGORITHM

  +-------------------+-------------------------------------------------------------+
  | Global Severity   | Defining Organ Score Criteria                               |
  +-------------------+-------------------------------------------------------------+
  | MILD              | * 1 or 2 organs involved with Score 1                       |
  |                   | * Lung score MUST be 0                                      |
  +-------------------+-------------------------------------------------------------+
  | MODERATE          | * 3 or more organs involved with Score 1                    |
  |                   | * OR At least 1 organ involved with Score 2                 |
  |                   | * OR Lung Score = 1                                         |
  +-------------------+-------------------------------------------------------------+
  | SEVERE            | * At least 1 organ involved with Score 3                    |
  |                   | * OR Lung Score = 2 or 3                                    |
  +-------------------+-------------------------------------------------------------+

Clinical Management Implications

NIH organ and global severity scores standardize description and longitudinal response; they do not independently prescribe one drug or dose. Limited mild disease may be managed with organ-directed therapy and close follow-up. Moderate, severe, progressive, lung, or function-threatening disease often warrants systemic treatment plus organ-directed care, rehabilitation and infection/toxicity prevention. Distinguish reversible activity from fixed damage and incorporate rate of progression, prior therapy, comorbidity, infection, quality of life and patient goals.

Pulmonary involvement and severe global scores carry important morbidity and mortality risk. New cough, dyspnea or spirometric decline requires prompt evaluation for infection, bronchiolitis obliterans syndrome and non-GVHD pulmonary causes rather than waiting for a routine visit.

4. Assessing the Organs the Score Depends On

NIH organ scoring is only as good as the examination behind it, and the ocular and oral domains are the ones most often scored from a general impression rather than from a measurement.

Eyes. Dry eye in chronic GVHD ranges from mild grittiness to corneal ulceration and vision loss. Scoring uses the patient-reported severity of symptoms, the impact on activities of daily living, and whether lubricant drops are needed more than a defined number of times per day. Tear production may be measured objectively with a Schirmer test, and ophthalmology evaluation is arranged for anything beyond mild disease, because the eye can deteriorate faster than any other scored organ and the damage is not always reversible.

Mouth. Oral chronic GVHD produces lichenoid changes, erythema, ulceration, mucoceles, and restricted mouth opening. Scoring reflects the extent of mucosal change and the degree to which oral intake is limited. Assess for reduced mouth opening, dental caries from xerostomia, and pain that is limiting nutrition, and involve oral medicine or dentistry rather than treating it as a comfort issue alone.

Both domains illustrate the general rule of NIH scoring: it grades functional impact, not appearance, so the question is always what the patient can no longer do.