A 60-year-old woman presented with painful, sclerotic hands and fingers due to progressive cutaneous scleroderma. She was started on a compounded topical cream containing ketamine, baclofen, gabapentin, verapamil, and pentoxifylline, which provided significant pain relief and improved sensation within a month. At a 6-month follow up, she had been largely weaned off opioid pain medications. The customized treatment targeted the pathophysiology of the condition and helped manage her debilitating symptoms.

1. SYSTEMIC
SCLEROSIS
NUR FARRA NAJWA
082015100035

2. LEARNING OBJECTIVES
At the end of seminar, student should be able to
• Define what is systemic sclerosis
• Know the type and the manifestation
• How to make clinical diagnosis and investigation needed
• The management for systemic sclerosis

3. INTRODUCTION
• @SCLERODERMA
• Generalised disorder of connective tissue
• Peak age of onset is in the fourth and fifth decades,
• Prevalence is 10–20 per 100 000,
• 4 : 1 female preponderance.
Skin
Internal organ
Vasculature Sclerodactyly
Digital ischaemia
Raynaud’s

6. TYPE
SYSTEMIC
SCLEROSIS
Limited cutaneous
systemic sclerosis,
LCSS: 70%
‘CREST’ syndrome
Diffuse cutaneous
systemic sclerosis,
DCSS: 30%
Poor prognosis
5year survival of
approximately
70%.

11. POOR PROGNOSIS FEATURES
• Older age,
• Diffuse skin disease,
• Proteinuria,
• High ESR,
• A low TLCO (gas transfer factor for carbon monoxide)
• Pulmonary hypertension

12. PATHOPHYSIOLOGY
• Genetic component
SEVERITY ISOLATED CASES
• Influences by race
• DCSS is significantly more
common in black women
than white.
• Systemic sclerosis-like
disease
• Triggered by exposure to
silica dust, vinyl chloride,
hypoxyresins and
trichloroethylene.

13. Cont.
• There is clear evidence of
immunological dysfunction:
o T lymphocytes, especially those of the Th17 subtype,

14. T lymphocyte
infiltrate the
skin…
Abnormal
fibroblast
activation
Leading to
increased
production of
extracellular
matrix in the
dermis,
primarily
type I
collagen.
Results in
symmetrical
thickening,
tightening and
induration of the
skin
(sclerodactyly)
Intimal
proliferation and
vessel wall
inflammation
cause to arterial
and arteriolar
narrowing.
Endothelial
injury causes
release of
vasoconstrictors
and platelet
activation,
resulting in
further
ischaemia,
which is
thought to
exacerbate the
fibrotic process.

17. CLINICAL FEATURES

18. • Nonpitting oedema of fingers and flexor tendon sheaths.
• Skin becomes shiny and taut, and distal skin creases
disappear.
• Erythema and tortuous dilatation of capillary loops in the
nailfold bed, readily visible with an ophthalmoscope or
dissecting microscope (and oil placed on the skin).
• The face and neck are usually involved next, with
thinning of the lips and radial furrowing.
• In some patients, skin thickening stops at this stage.
• Skin involvement restricted to sites distal to the elbow or
knee (apart from the face) is classified as ‘limited disease’
or CREST syndrome
• Involvement proximal to the knee and elbow and on the
trunk is classified as ‘diffuse disease’.
Skin

20. •Universal feature
•Can precede other features by many
years.
•Involvement of small blood vessels in
the extremities may cause critical
tissue ischaemia
•Leading to skin ulceration over
pressure areas, localised areas of
infarction and pulp atrophy at the
fingertips.
Raynaud’s
phenomenon

23. • Arthralgia,
• Morning stiffness
• Flexor tenosynovitis are common.
• Restricted hand function is due to
skin rather than joint disease and
erosive arthropathy is
uncommon.
• Muscle weakness and wasting can
occur due to myositis.
Musculoskeletal
features

25. • Smooth muscle atrophy and fibrosis in the lower two thirds
of the oesophagus lead to reflux with erosive oesophagitis.
• Dysphagia and odynophagia may also occur.
• Involvement of the stomach causes early satiety and
occasionally outlet obstruction.
• Recurrent occult upper gastrointestinal bleeding may
indicate a ‘watermelon’ stomach (antral vascular ectasia),
which occurs in up to 20% of patients.
• Small intestine involvement may lead to malabsorption due
to bacterial overgrowth and intermittent bloating, pain or
constipation.
• Dilatation of large or small bowel due to autonomic
neuropathy may cause pseudo-obstruction with nausea,
vomiting, abdominal discomfort and distension, often worse
after food.
Gastrointestinal
involvement

26. • Major cause of morbidity and mortality.
• Pulmonary hypertension complicates long-
standing disease common in LCSS than in
DCSS.
• It presents with rapidly progressive
dyspnoea (more rapid than interstitial lung
disease), right heart failure and angina, often
in association with severe digital ischaemia.
• Fibrosing alveolitis mainly affects patients
with dcss who have topoisomerase 1
antibodies
Pulmonary
involvement

27. • Main causes of death is
hypertensive renal crisis,
• Characterised by rapidly
developing malignant
hypertension and renal failure.
• Hypertensive renal crisis is much
more likely to occur in DCSS than
in LCSS, and in patients with
topoisomerase 1 antibodies
Renal
involvement

28. INVESTIGATIONS
• Clinical diagnosis
• Various laboratory abnormalities are
characteristic.
 The ESR is usually elevated
 Raised levels of IgG are common
 CRP values tend to be normal unless there is severe organ involvement
or coexisting infection.
 ANA is positive in about 70%
 30% of patients with DCSS have antibodies to topoisomerase 1 (scl70).
 60% of patients with crest syndrome have anticentromere antibodies

29. MANAGEMENT
• No treatments are available that halt or reverse
the fibrotic changes that underlie the disease.
• The focus of management,
o To ameliorate the effects of the disease on target organs.
1. Raynaud’s syndrome and digital ulcers.
2. Oesophageal reflux
3. Hypertension
4. Joint involvement
5. Pulmonary hypertension

30. Raynaud’s syndrome and digital
ulcers.
• Avoidance of cold exposure
• Use of mittens (heated mittens are available),
• Supplemented with calcium antagonists.
• Intermittent infusions of prostacyclin may benefit severe
digital ischaemia.
• The endothelin 1 antagonist bosentan can be of value in
promoting healing of digital ulcers.
• If become infected, antibiotics may be required, but
need to be given at higher doses for a longer duration
than usual

31. Oesophageal reflux
• Treated with proton pump inhibitors and antireflux
agents.
• Antibiotics may be required for bacterial overgrowth
syndromes,
• Metoclopramide or domperidone may help patients
with symptoms of pseudoobstruction.

32. Hypertension
• Treated aggressively with ACE inhibitors, even if renal
impairment is present.

33. Joint involvement
• Treated with analgesics and/or NSAID.
• If synovitis is present, immunosuppressants such as
methotrexate can also be of value

34. Pulmonary hypertension
• Treated with bosentan.
• In selected patients, heart–lung transplantation may be
considered.
• Corticosteroids and cytotoxic drugs are indicated in patients who
have coexisting myositis or fibrosing alveolitis

35. CASE

36. • A 60-year-old woman presented with painful and sclerotic hands
and fingers. She had been an airline attendant but had to quit her
job as a result of the pain and her inability to use her hands over
the past 7 years.
• History. The patient recently had been seen by a pain physician,
had been started on opioids, and had received stellate ganglion
blocks that had yielded very little relief. A rheumatologist had
prescribed methotrexate and corticosteroids in an attempt to stop
excessive overproduction of connective tissue and to help control
her disease state, which also did not help. She had opted out of
tacrolimus therapy, which can soften the fibrosis but also is
associated with an increased risk of malignancy.1
• Physical examination. The patient had no lung or heart
problems or complaints. No vascular abnormalities or
telangiectasia were seen on examination. Her fingers were
unable to be opened or flexed and were wooden-like on
palpation; some digits were missing from self-amputation with
chronic pain (Figures 1 and 2).

37. Figure 1. The patient's hands at presentation

38. Figure 2. A photograph of the patient’s hands 15 years before presentation.

39. • The woman received a clinical diagnosis of progressive cutaneous scleroderma.
• Discussion. Localized scleroderma has an estimated prevalence of 50 per
100,000 before age 18 years and 220 per 100,000 by age 80.1 Scleroderma is a
chronic autoimmune disorder that is manifested by excess synthesis and
deposition of collagen in skin and connective tissue.1
• Vascular abnormalities occur as Raynaud phenomenon and swelling of the acral
portions of the extremities, with thickening of the skin of the fingers as the most
common complaints in CREST syndrome (calcinosis, Raynaud phenomenon,
esophageal dysfunction, sclerodactyly, and telangiectasia). Cutaneous
manifestations were the only findings present in our patient’s case. Generalized
scleroderma, on the other hand, can affect the cardiovascular and pulmonary
systems; kidney failure may occur in severe cases.2
• The usual skin presentation in progressive localized scleroderma includes sclerotic
fibroblasts (myofibroblasts) in the dermis that are capable of multiple replicative
passages; this often affects the arms, face, and legs.3 The skin in affected areas
often takes the form of morphea—patches or linear bands that become thick, hard,
and discolored.2,3 Morphea usually is not progressive; however, if it is progressive,
as in progressive cutaneous scleroderma, it may lead to disfiguring and debilitating
deformities, especially in the limbs.

40. Outcome of the
case. Consultation with a
pain psychologist was
recommended to help the
woman cope with her
painful hands and to help
her be more independent,
including managing even
simple everyday
activities. She also
obtained custom-made
utensils (Figure 3) and
other items of daily
living.Figure 3. Custom utensils such as this spoon were
fashioned to help the woman eat

41. • A topical compounded cream containing 10% ketamine, 2% baclofen, 6% gabapentin, 6%
verapamil, and 3% pentoxifylline also was started, focused on reducing fibrosis and
peripheral neuropathy.3 Within a month of using this cream, the patient noticed remarkable
improvement in sensation and pain, so much that we were able to begin weaning her from
chronic opioid therapies. At a 3-month follow-up visit, she was visually excited and tearful,
reporting that “the cream is the only thing that truly works for my hands.” She reported
“feeling her fingers again” as an indicator that her hand pain and sclerotic/fibrotic digits had
some return of sensation.
• The compounded cream’s active ingredients, which address the vascular perfusion and
inhibition of certain receptors (pentoxifylline)4 and the up-regulation of collagenase and
collagen breakdown (verapamil),5 in conjunction with the regulation of calcium channels
and pain transmitters (gabapentin and ketamine)6-8 and potential improvements in soft
tissue relaxation with analgesic properties (baclofen),9 make this combination very
effective.
• Physical therapy would have been an appropriate treatment prior to self-fusion of her
joints; however, at this stage the joints are fused and sclerotic. Opioids should be viewed
as a means of pain control when other conservative therapies and medications have failed.
Spinal cord stimulation could be a good final option to help with the neurogenic pain, given
the responses to the stellate blocks if topical therapy were ineffective.
• Six months into her continued daily use of the compounded cream, the patient had been
weaned from most of her short-acting hydrocodone/acetaminophen and had completely
discontinued fentanyl.

42. SUMMARY
• Define what is systemic sclerosis
• Know the type and the manifestation
• How to make clinical diagnosis and investigation needed
• The management for systemic sclerosis

43. REFERENCES
• DAVIDSON 19TH EDITION
• http://www.e-ijd.org/article.asp?issn=0019-
5154;year=2013;volume=58;issue=4;spage=255;epage=
268;aulast=Viswanath
• https://emedicine.medscape.com/article/331864-
overview#a3