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5.1 Introduction
Onychomycosis is a common nail infection that
affects millions of people worldwide with a
prevalence of up to 13% [1–7]. Although there
are good treatments for onychomycosis, pharmaceutical companies continue to study new
compounds and vehicles with hopes of finding
the magic bullet for onychomycosis eradication.
Clinical trials for onychomycosis drugs require
standardized fungal nail assessment that is meaningful, reproducible, accurate, and consistent
across a wide range of investigators performing
the clinical trials.
5.2 Methods for Grading
There are many variations on onychomycosis
treatment efficacy endpoints in onychomycosis
trials. The process of grading fungal nails to
assess the efficacy of an investigational product for onychomycosis continues to evolve.
Inclusion and exclusion criteria in clinical trials
help assure that subjects with similar characteristics are randomized within and across all
investigative sites in the trial. Inclusion criteria
involving the target nail – such as the type of
onychomycosis, percent of involvement, thickness of nail involved, presence or absence of
yellow spikes, and lateral nail and matrix
involvement – attempt to assure uniformity of
subjects. This standardization of subjects in
trials is important for assessing efficacy in a
standardized and reproducible fashion. It also
will ultimately allow clinicians to choose the
best treatment on an individualized basis
depending on the type and extent of their
patient’s nail disease. Standardized patient characteristics as defined in the protocol exclude
subjects who are outside an age range, or have
specific comorbidities such as immune compromise, diabetes, and tinea pedis (Box 5.1).
Photographs of target nails are routinely taken
at study visits and a central grader is sometimes
used to determine subjects’ nail eligibility
from the photographs. Notching of nail and
planimetry (digital comparison of outlined area
of nail fungal involvement) has been used in
some studies for efficacy endpoint measurement.
5
Grading Onychomycosis
Anna Q. Hare and Phoebe Rich*
Department of Dermatology, Oregon Health and Science University, Portland, OR, USA
*Corresponding author: Phoebe Rich
42 Onychomycosis
Nails may be notched to assure adequate nail
growth prior to randomization and to assess
unaffected nail plate length during treatment
(Figure 5.1).
Several onychomycosis scales have been proposed in the past but are not widely used. Sergeev’s
scale [8] assigned a numeric value based on
clinical form, duration of disease, degree of
thickening,and age of patient (to calculate rate of
nail growth). Baran et al. [9] published a severity
scale for onychomycosis using 10 clinical, patient‐,
and organism‐specific features that predicted the
likelihood of a treatment outcome, rather than
grade severity. Neither of these two systems has
yet been validated.
The Onychomycosis Severity Index (OSI), a
validated onychomycosis assessment scale, was
recently developed and published by consensus
group of nail experts [10]. This user‐friendly
assessment tool uses salient clinical features of a
diseased nail to arrive at a numeric value that
corresponds to disease severity. The OSI uses
three clinical features to assess severity on a
scale of 0–4:
1) Area of involvement
2) Proximity of disease to the nail matrix
3) Occurrence of dermatophytomas and subungual hyperkeratosis thickness of > 2 mm.
Percent involvement is estimated using the
formula of 1 point for 11–25%, 3 points for 26–50%, 4 points for
41–75%, and 5 points for > 75% involvement.
In some cases, percent involvement can be
difficult to assess either due to clipping back of
onycholytic nail or, in the case of chronic
onycholysis, the distal nail bed has become
keratinized with presence of dermatoglyphs. In
these cases, involvement is based on the projected original nail bed, measured either from
the distal groove if present and obvious or from
estimation based on anatomy.
Proximity to the matrix is determined by
the most proximal quadrant of the nail that
has visible fungal elements using the following
guidelines. The nail is divided transversely
into five equal segments and a numeric value
of 1 to 5 assigned to the segments with 1 given
to the quadrant involving the free edge
(Figure 5.2). The quadrant that contains the
most proximal edge of the onychomycosis is

Figure 5.1 Notched onychomycosis‐affected nail. Many
studies notch the nail to monitor growth.
Grading Onychomycosis 43
the number assigned to characterize the proximity of disease to matrix.
Dermatophytoma and subungual hyperkeratosis are both poor prognostic factors in
onychomycosis, representing a high fungal burden [11]. Dermatophytoma is essentially a fungal abscess, and is typically characterized by a
yellow or orange‐brown longitudinal streak or a
patch visible in the nail, typically occurring near
the lateral nail fold (Figure 5.3). As streaks can
be confused with onycholysis, a true dermatophytoma streak does not usually extend to the
free edge of the nail plate.
Subungual hyperkeratosis, a thickening of the
stratum corneum due to fungal infection, is also
considered a poor prognostic sign. This is
thought to be due to difficulty in penetration of
topical agents through the thickened nail and
higher fungal burden [9, 11]. A cutoff of 2 mm,
measured from the nail bed to the ventral surface of the nail plate, is used to judge the effect
of subungual hyperkeratosis (Figure 5.4). This
measurement does not include the nail plate
itself. Both subungual hyperkeratosis > 2 mm
and the presence of a dermatophytoma represent high fungal burden, thus either of these features or both earns an additional 10 points, but
not more.
5.3 Using the OSI Scale
The nail is assessed for area of involvement 0–5,
multiplied by the proximity‐to‐the‐matrix score,
plus an additional 10 points for the presence of
1
5
4
3
2
Figure 5.2 Grading proximity to the matrix. This nail
would be graded as a 4 because the most proximal
involvement falls in the fourth quadrant.
Figure 5.3 Distal lateral subungual onychomycosis
(DLSO) with dermatophytoma. Note the yellow, dense
blotches identifying the several dermatophytomas.
Figure 5.4 Distal subungual onychomycosis with
subungual hyperkeratosis. The hyperkeratosis would be
measured from nail bed to bottom of nail plate,
considered significant if > 2 mm.
44 Onychomycosis
one or more streaks and/or a thickness of>2mm.
The final value determines the severity of the nail
disease. The highest score possible for each nail is
35 (Box 5.2).
The final score designates the severity category of disease. A score of 5 or less indicates
mild disease, 6–15 indicates moderate disease,
and 16 or more indicates severe disease. An
unaffected nail or one appearing clinically
cleared of disease has a score of 0.
The OSI scoring system is both user‐friendly
and highly consistent between graders. Subtle
differences in grading of severity are temporized by the multiplication factor of proximity
to the matrix, yielding high inter‐operator consistency. This scoring system was validated by
two different assessments yielding consistently
high inter‐rater reliability (Cronbach 0.95–0.99,
ICC 0.93–0.98) [10].
References
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2 Ghannoum MA, Hajjeh RA, Scher R, et al. A
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American Academy of Dermatology. 2000;
43(4): 641–648.
3 Svejgaard EL, Nilsson J. Onychomycosis in
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4 Roberts DT. Prevalence of dermatophyte
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5 Perea S, Ramos MJ, Garau M, et al. Prevalence
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