SAN PEDRO COLLEGE

Bachelor of Science in Medical Laboratory Science

LIMITED CUTANEOUS SYSTEMIC SCLEROSIS

A Case Study in

IMMUNOLOGY & SEROLOGY LABORATORY

BSMLS 3G – 5

Araral, Maxine C.
Dionela, Myka Ella Audriey C.
Impuerto, Kissan M.
Juanitez, Jerameel G.
Pascua, Stephany May G.
Ramirez, Vher John L.
Umbay, Chricy Queenie Mae P.
OBJECTIVES OF THE STUDY

The study aims to:

1.) Determine the exact diagnosis of the patient.
2.) Discuss the disease that affects the patient
3.) Correlate the history of the patient to that of the diagnosis.
4.) Provide supporting facts that the patient's diagnosis is disease-associated
base on the laboratory results.
5.) Provide recommendations for the patient, their relatives, and the clinicians
involved with the disease.
 CHAPTER I

INTRODUCTION TO THE CASE

Scleroderma or systemic sclerosis (SSc) is a chronic autoimmune disease of the

connective tissue and other organs, characterized by the stiffening of the skin that usually
occurs in women aged 30-50 years old with a ratio of 4.6:1 from that of men. The word
scleroderma is rooted from two Greek words, "sclera," meaning hard, and "derma," which
means skin. SSc is classified as limited cutaneous SSc or diffuse cutaneous SSc, which
depends based on skin involvement.

Limited cutaneous SSc is associated with the presence of Raynaud's phenomenon for
years or decades, dilation of the nail fold capillary loops, and skin stiffening limited to the
hands, face, feet, and forearms. The said type is also called CREST Syndrome, which stands
for having Calcinosis, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly, and
Telangiectasia. On the other hand, diffuse cutaneous SSc is characterized by the presence of
tendon friction rubs, truncal and acral skin tightness, and the onset of Raynaud's phenomenon
within the same year of having skin changes. Another symptom that can support this
classification is having interstitial lung disease, oliguric renal failure, diffuse gastrointestinal
disease, and myocardium, unlike the limited cutaneous, which has the late occurrence of
some of the symptoms.

The said classification is based on the criteria established in the year 1980 by the
American Rheumatism Association, which is now referred to as the American College of
Rheumatology (ACR). Based on the ACR classification, SSc's incidence and prevalence rate
account for 32 and 254 cases per million, respectively.

The cause of this said disease is not fully understood. Thus doctors have difficulty in
diagnosing this type of condition. However, several studies revealed that SSc could be
associated with genetics. In a study conducted by Nguyen et al., HLA markers and anti-RNA
polymerase III have a predictive role in developing scleroderma renal crisis. Also,
environmental factors such as exposure to silica dust particles trigger the development of
signs and symptoms that vary from patient to patient. As seen in 95% of patients developing
scleroderma, Raynaud's phenomenon is the most common manifestation.

Different tests are carried out to confirm the diagnosis, such as screening for
antinuclear antibodies (ANA), specifically the anti-centromere and the anti-topoisomerase
antibodies, nail fold capillaroscopy High-resolution computerized tomography (HRCT) of the
chest, hand X-ray, and esophageal manometry. Anent to these tests, it is also necessary to
perform complete blood count, renal and liver functions, electrocardiogram, and NT-pro-BNP
dosage to detect associated diseases to prevent it from developing into further complications
which could even lead to death.
 CHAPTER II

PATIENT’S CLINICAL DATA WITH HISTORY

Patient Information:
• 52 years old
• Female

Patient History:
• Raynaud’s phenomenon for 15 years
• Blanching and cyanosis of fingertips on cold exposure
• Progressing noticeable digital ischemia
• Painful sores on several finger pads:
o With white, chalky material extrusions
o Slow to heal
• Dysphagia
• Heartburn
• Gastrointestinal symptoms:
o Esophageal dysmotility
- Found out through barium swallow
- Under proton-pump inhibitor therapy

Patient Manifestations:
• Nausea
• Headache
• Vomiting for 2 days
• Abdominal pain

• Vital Signs:
o Body temperature – 36.6⁰C
o Pulse rate – 80 beats per minute
o Respiration rate – 14 cycles per minute
o Blood Pressure – 120/80 mmHg

• Physical Examination:
o Skin:
- Puffy fingers with loss of skin creases over dorsum distal fingers
- Shallow digital pitted scars on several finger pads, some with
ulceration and chalky white exudate
o Chest:
- No adventitial breath sounds
o Cardiac:
- Regular rate and rhythm
- Normal heart sounds

o Abdomen:
- Nondistended and nontender
o Extremities:
- No edema
o Musculoskeletal:
- Mild flexion contractures of fingers with inability to flatten hand
- No joint tenderness or swelling
- Firm, nontender subcutaneous nodules overlying each elbow
Laboratory Tests: Test Result: Interpretation:
 HEMATOLOGY
 Hemoglobin 13.3 g/dL NORMAL
 Hematocrit 39.9 L/L NORMAL
 RBC count 4.4 x 1012/L NORMAL
 WBC count 18 x 109/L ABOVE NORMAL
▪ Neutrophils 35% BELOW NORMAL
▪ Lymphocytes 45% ABOVE NORMAL
▪ Eosinophils 4% ABOVE NORMAL
▪ Basophils 1% ABOVE NORMAL
▪ Monocytes 15% ABOVE NORMAL
 Platelets 152 x 109/L NORMAL
 ESR 35 mm/hr ABOVE NORMAL

 CHEMISTRY
 FBS 4.5 mmol/L NORMAL
 SUA 375 umol/L NORMAL
 Creatinine 0.88 mg/dL NORMAL
 SGPT 41 U/L ABOVE NORMAL
 HbA1C 4.7 % NORMAL

 SEROLOGY
 Rheumatoid Factor 11 IU/mL NORMAL
 ANA (Qualitative) Centromere pattern
 CRP 5.9 mg/L ABOVE NORMAL

 URINALYSIS
 Color Light yellow NORMAL
 Transparency Hazy
 Protein Trace
 Glucose - NEGATIVE
 pH 6.0 NORMAL
 Specific gravity 1.015 NORMAL
 Pus cells 1-3/hpf ABOVE NORMAL
 RBC 2-4/hpf ABOVE NORMAL
 Mucus threads + POSITIVE
 Epithelial cells + POSITIVE

Radiographic Test Results:

 Hand Radiograph
o Focal, dense well-defined calcifications in the soft tissues of multiple distal
fingertips
o No joint erosions

 Chest Radiograph
o Clear lung fields and normal cardiac size
o IMPRESSION: Normal chest

 Echocardiogram:
o Normal LV ejection fraction
o Normal RA and RV dimensions
o No tricuspid regurgitation present
▪ Estimate of RSVP not possible
 CHAPTER III

A. DEFINITION OF THE CASE

Limited Cutaneous Systemic Sclerosis

is an autoimmune condition which is a subtype
of systemic sclerosis. It is characterized by
Raynaud's phenomenon and skin fibrosis,
where there are changes in the skin's physical
appearance and texture. This is attributed to
the increased production of collagen. Collagen
is a portion of connective tissue that affects
the skin to tighten distal to the elbows, knees,
and face. This disorder is also limited only to
skin changes and other organs such as blood
vessels, muscles, heart, digestive system,
lungs, and kidney.

As the condition progresses, signs and symptoms of having Systemic Sclerosis can be
observed and may vary depending on which part of the patient's body is affected. These may
include nausea, headache, vomiting, and abdominal pain. Symptoms may be referred to as
CREST. One of the early signs of systemic scleroderma that can be seen on fingers and toes
is Raynaud's disease, which causes the blood vessels in your fingers and toes to compress
when you are in a cold environment or emotional distress. When this occurs, the blood cannot
penetrate the skin's surface, and the affected parts turn white and blue. Patients with this
disorder may experience myriad systemic complications. Most patients with systemic sclerosis
may only encounter mild symptoms. This is a long-term condition, but it rarely causes severe
complications with internal organs.

The peak age at the onset of systemic sclerosis (SSc) is between 20 and 50 years,
whereas SSc is also identified in young and older people. The predicted course of limited
cutaneous sclerosis is relatively good with a long-lasting disease period (10-year survival rate
is about 80% to 90%). However, pulmonary arterial hypertension can be a consequence of
this condition, leading to a more serious prognosis. Serious lung fibrosis can occur in some
cases. Patients are most at risk for esophageal dysmotility (67%), interstitial lung disease
(37%), and isolated pulmonary artery hypertension (31%).

The physical examination shows that the patient has normal vital signs. The fingers
appear to be puffy with the absence of skin creases over the dorsum of distal fingers and
superficial digital scars on certain finger pads. Other fingers are with ulceration and chalky
white exudation with the failure to flatten hands on the table; no joint swelling and erosions.
The abdomen was not affected, and there was no edema on the extremities.

The patient in this case study is a 52 years old female with a 15-year history of
Raynaud's phenomenon with digital pitted scars, dysphagia, heartburn, and esophageal
dysmotility. Significant laboratory findings are mostly normal in the Complete Blood Count
(CBC) with slightly above normal values for the WBC count and ESR. Chemistry and serology
results are normal. The positive antinuclear antibody (ANA) with a centromere pattern also
supported the diagnosis. The chest shows a clear lung field, normal cardiac size, and normal
heart movement based on radiographic tests.
B. ANATOMY AND PHYSIOLOGY

I. SKIN

The skin, also known as the integument or cutaneous layer, is a protective barrier that
covers the body's external surface and is considered the largest organ of the human
anatomy. The skin comprises 7% of total body weight in adults, covering about 2 square
meters, and weighs 4.5–5 kg. The skin mainly consists of two parts: the outermost layer
consisting of epithelial cells, epidermis, and the deeper, thicker fibrous layer that supports
and strengthens the epidermis, dermis. Also, beneath the dermis lies a subcutaneous layer
of fat, also known as hypodermis. Although it is not part of the skin per se, it supplies
nutrients to the other two layers and provides cushion and insulation to the body.

i. EPIDERMIS

Histologically, the epidermis is made up of keratinized stratified squamous

epithelium. It primarily consists of 4 types of cells: keratinocytes, melanocytes,
intraepidermal macrophages, and tactile epithelial cells.

● Keratinocytes: produces keratin that shields the skin and underlying tissues from
abrasions, heat, microbes, and chemicals. It also regulates water content by
releasing a water-repellent sealant and inhibits the entry of foreign materials.

● Melanocytes: synthesizes a yellow-red or brown-black pigment called melanin

that provides color to the skin and protects it from ultraviolet radiation. The
pigment melanin is transferred to keratinocytes via the long, slender projections
of melanocytes. The melanin then surrounds the nucleus to protect the DNA from
damage by UV light.

● Intraepidermal macrophages: also known as Langerhans cells, participate in

immune responses mounted against microbes that invade the skin by acting as
antigen-presenting cells.
 ● Tactile epithelial cells: also known as Merkel cells; can be found in the deepest
layer of the epidermis, reaching a flattened process of a sensory neuron (nerve
cell), a structure called a tactile disc or Merkel disc, hence serving as
mechanoreceptors.

The stratification of the epidermis shows the distinct stages of development of

keratinocytes. It varies from 4-5 depending on the type of skin, either thin or thick.
The former has 4 layers-stratum basale, stratum spinosum, stratum granulosum, and
a thin stratum corneum; the latter has areas greatly exposed to, including an
additional layer, stratum lucidum. The following shows the layers going from deep to
superficial:

● Stratum Basale: the deepest layer, also known as stratum germinativum it

consists of stem cells, hence undergoing mitosis throughout life. It is composed of
keratin that shields the deeper layer from damage and keratin intermediate
filaments attached to desmosomes—this anchor the cells of stratum basale
together and to its adjacent stratum spinosum.

● Stratum Spinosum: This layer contains post-mitotic cells from stratum basale
and keratin intermediate filaments arranged into spine-like projections that are
inserted into desmosomes, hence known as the “prickly layer.” This gives strength
and flexibility to the skin.

● Stratum Granulosum: This layer comprises three to five layers of flattened

keratinocytes due to apoptosis. The increased distance from their source of
nutrition causes the degeneration of their nuclei and other organelles apoptosis.
Distinct cells within this layer include keratohyalin and lamellar granules.
Keratohyalin arranges keratin intermediate filaments into keratin, whereas the
latter begin to release a lipid-rich secretion that acts as a water sealant. This marks
the transition towards the more superficial strata consisting of dead cells.

● Stratum Lucidum: This layer is only found in thick skin areas, such as soles,
palms, and fingertips. It has 4-5 layers of flattened clear, dead keratinocytes, which
gives an additional level of toughness in this region of thick skin due to abundant
keratin and thickened plasma membranes present.

● Stratum Corneum: This layer is the final product of keratinization. It is composed

of fragile, flat, plasma membrane-enclosed keratin packages devoid of a nucleus
or any internal organelles. As cells continuously slough off, they are replaced by
cells from deeper strata. This layer's thickness varies from a few cells in thin skin
to 50 or more cell layers in thick skin, but on average, it has 25 to 30 layers. This
protects from injury and microbial invasion. Once exposed to constant friction, a
callus is formed.

ii. DERMIS

The second, deeper layer of skin supports the epidermis and binds it to the
subcutaneous tissue. It is composed of dense irregular connective tissue containing
collagen and elastic fibers. Both fibers are held together by a mixture of glycoproteins,
bound water, and glycosaminoglycans. This connective tissue network is strong
enough to hold the skin together. It still allows epidermal appendages,
neurovasculature, and lymphatics to pass through its substance. It is made up of two
definitive layers: Papillary and Reticular Layer:
 ● Papillary Layer: the more superficial layer of the two. It is characterized by small,
nipple-shaped projections in the undersurface of the epidermis called dermal
papillae interlaced with epidermal ridges. All dermal papillae contain capillary loops
(blood vessels), while some have nerve endings called corpuscles of touch or
Meissner corpuscles. Also, type VII collagen runs deep in the papillary dermis and
therefore provides mechanical stability to the epidermal substratum. Overall, it
gives mechanical support and metabolic sustenance.

● Reticular Layer: The deeper, thicker layer contains bundles of thick collagen
fibers, scattered fibroblasts, and various wandering cells. It gives the skin strength,
extensibility, and elasticity, given its composition of both collagen and elastic
fibers. The reticular layer has topographical landmarks, known as cleavage lines,
which correspond to dermal collagen fibers' orientation.

Structural Basis of Skin Color

Skin color varies from person to person, depending on the three pigments: melanin,
hemoglobin, and carotene.

 Melanin: Typically, humans have about the same number of melanocytes. They only
differ in the amount of pigment produced. Within a melanosome, melanin is
synthesized from the amino acid tyrosine in the presence of an enzyme called
tyrosinase. Its amount produced corresponds to a skin color varying from pale yellow
to reddish-brown to black. It has two types: pheomelanin, which ranges from yellow-
red, and eumelanin, ranging from brown-black. Upon exposure to UV rays, the melanin
absorbs it to protect the DNA from damage and neutralizes free radicals following the
damage.

 Hemoglobin: In light-skinned individuals, the epidermis appears translucent. Hence,

hemoglobin, the blood's oxygen-carrying capacity, causes skin color to range from
pink to red. Basically, the pigmentation corresponds to the oxygen content of the blood
moving through capillaries in the dermis.

 Carotene: a pigment that gives off yellow-orange pigmentation, seen in egg yolks and
carrots. This is a precursor of Vitamin A, which is a necessary component needed for
vision. The excessive diet causes it to be stored in the dermis and subcutaneous layer's
stratum corneum and fatty areas.

Accessory Structures of Skin

Hair, skin glands, and nails are structures that embryologically originate from the epidermis
and are often termed "appendages." They can extend down through the dermis into the
hypodermis. They have a host of important functions in the body.

 Hair: a structure growing out of the epidermis, made up of keratin. It is found on all
areas of the body except the hands' palms, soles of the feet, and the lips. It consists
of a hair shaft, mostly superficial to the surface, a hair root that penetrates the dermis
and sometimes the subcutaneous layer, and a hair follicle. The hair offers a limited
amount of protection—from the sun, heat loss, and foreign particles' entry into the
eyes, nose, and ears. They also function in sensing light touch.
  Skin glands: categorized into sebaceous, sudoriferous glands, and ceruminous
glands.

a. Sebaceous glands (Oil glands): Simple, branched acinar (rounded) glands

connected to hair follicles. Its secreting portion is found in the dermis and opens
to the neck of hair follicles, except some locations, such as the lips, glans penis,
labia minora, and tarsal glands of the eyelids, where it opens directly to the skin.
They are basically all over the body except for the palms and soles. The oily
substance they secrete, sebum, prevents the drying and brittleness of hair.
Furthermore, it keeps water from evaporating excessively from the skin, gives
the pliability and softness of skin, and inhibits the growth of some bacteria.

b. Sudoriferous glands (Sweat glands): These glands release sweat, or

perspiration, into hair follicles or onto the skin surface via pores. It has two main
types, (1) eccrine and (2) apocrine. They are categorized based on their structure
and type of secretion. The Eccrine are simple, coiled tubular glands. The sweat it
secrets consists primarily of water, with small ions, urea, uric acid, ammonia,
amino acids, glucose, and lactic acid. It serves in thermoregulation by
evaporation. It is found in the skin of most regions of the body, especially in the
skin of the forehead, palms, and soles. Whereas the apocrine gland, despite
having the same gland structure, has bigger ducts and lumens. The apocrine
sweat has the same components as eccrine but with lipids and proteins, unlike
the odorless eccrine sweat. Apocrine sweat interacts with the bacteria on the skin
surface, hence releasing a musky odor.

c. Ceruminous glands: Modified sweat glands in the external ear. The combined
secretion of the ceruminous and sebaceous glands is a yellowish material called
or earwax. Cerumen, together with hairs in the external auditory canal, provides
a sticky barrier that impedes foreign bodies and insects' entrance. Cerumen also
waterproofs the canal and prevents bacteria and fungi from entering cells.

 Nails: made up of hardened and densely packed keratin, which covers our fingers'
dorsal surfaces and toes from mechanical damage. It is principally made up of a nail
body, free edge, nail root, lunula, hyponychium, nail bed, eponychium, and nail matrix.
The nail body is the visible, translucent portion of the nail. Its pinkish appearance is
attributed to the flowing blood in the capillaries underlying the dermis. Its extension
is called the free edge. The nail root is the buried portion under the skin folds. The nail
bed is the skin below the nail plate that extends from the lunula to the hyponychium.
The lunula forms the crescent-shaped area of the nail body's proximal end, while the
hyponychium is a thickened portion of the stratum corneum that secures the nail to
the fingertips. Found at the nail's proximal end is a fold of the skin called eponychium,
also known as the cuticle. Lastly, the production of new nails takes place in the nail
matrix.

Overall, the skin has many diverse roles:

✓ It serves as a physical barrier from friction and potential pathogens, and protects the
body from water loss and ultraviolet radiation using pigment cells, melanocytes;
✓ Acts as a channel of communication to the external environment;
✓ Insulates the body (the fatty layer and hair on the head) and also accelerates heat
loss (sweat production and a dense superficial microvasculature);
✓ Participates in calcium homeostasis by contributing to the body's supply of vitamin D;
 ✓ Visual indicators of health involved in the attraction between the sexes such as skin
pigmentation, hair, and sex pheromones by the apocrine sweat glands and other skin
glands.

II. The Gastrointestinal Tract

The Gastrointestinal Tract, also known as the alimentary canal, is a series of hollow
organs joined in a long, twisting tube from the mouth to the anus. Specifically, it includes
the mouth, most pharynx, esophagus, stomach, small intestine, and large intestine. The
length of the GI tract is about 5–7 meters, wherein the food, from the time it is eaten, is
digested and absorbed or eliminated. Muscular contractions in the wall of the GI tract
physically break down the food by churning it and propelling the food along the tract.

The wall of the GI tract is made up of four layers with the same basic arrangement
starting from the lower esophagus to the anal canal. The layers are the mucosa,
submucosa, muscularis, and serosa/adventitia from deep to superficial.

 Mucosa: a mucous membrane found in the inner lining of GIT which consists of (1) a
layer of the epithelium in direct contact with the contents of the GI tract, (2) a layer
of connective tissue called the lamina propria, and (3) a thin layer of smooth muscle
(muscularis mucosae). It secretes sticky mucus in the Gi tract through specialized
goblet cells, as well as small finger-like structures called villi and microvilli, which
enhance surface area. Basically, it functions in absorption and secretion.

 Submucosa: anchors the mucosa to the muscularis with its areolar connective tissue.
It is a relatively thick layer that contains submucosal plexus, an extensive network of
neurons. It is highly vascular; thus, it receives the absorbed food molecules.

 Muscularis: includes skeletal muscles involved in voluntary contractions for

swallowing such as, the mouth, pharynx, and superior and middle parts of the
esophagus. It is found in the anal sphincter during defecation as well. Meanwhile, it
also includes involuntary contractions of smooth muscles all throughout the GI tract
for breaking down, digestion, and propulsion of food along the tract.
  Serosa: a serous membrane composed of areolar connective tissue and mesothelium.
It makes up the superficial layer of suspended portions of the GI tract in the abdominal
cavity and a portion of the peritoneum. Hence it is called the visceral peritoneum. The
mesothelium secretes the lubricating serous fluid in order to minimize friction from
muscle movements.

Major Components of GI Tract

→ Mouth: also called as the oral or buccal cavity, structurally consists of the cheeks,
hard and soft palates, and tongue. Along with its associated muscles, the tongue forms
the floor of the oral cavity. It is composed of mucous membrane wrapped around the
skeletal muscle, while its upper surface and sides are covered with papillae, some of
which contain taste buds. Lingual lipase, secreted from the glands of the tongue,
digests triglycerides into fatty acids and diglycerides once it reaches the stomach's
acidic environment. Furthermore, major salivary glands lie outside the mouth and pour
their contents into ducts that empty into the oral cavity. The major salivary glands
consist of parotid, submandibular, and sublingual glands. The production of saliva
lubricates food and triggers the chemical digestion of. Meanwhile, mechanical digestion
occurs by the teeth projecting into the mouth. It includes three principal regions:
crown, root, and neck. They are classified into two dentitions: deciduous and
permanent. Teeth are made up of dentin and are wrapped by enamel, the hardest
substance in the body.

→ Pharynx: a tube that extends from the internal nares to the esophagus posteriorly
and the larynx anteriorly characterized by its funnel-like shape. It consists of three
parts: the nasopharynx, the oropharynx, and the laryngopharynx. Both the
oropharynx and laryngopharynx have digestive and respiratory functions, while the
nasopharynx serves only in respiration. As food travels from the mouth into the
oropharynx and laryngopharynx, it is propelled into the esophagus and then into the
stomach via muscle contraction.

→ Esophagus: Located posterior to the trachea, this 10-inch collapsible muscular tube
secretes mucus and transports food into the stomach. It facilitates deglutition along
with the mouth and pharynx. It is composed of two sphincters: the upper esophageal
sphincter, which regulates food movement from the pharynx to esophagus, and the
lower esophageal sphincter, that regulates the food passage from esophagus to the
stomach. Superficially, it consists of adventitia, which attaches the esophagus to its
surrounding structures.

→ Stomach: Bridging the esophagus to the duodenum, is a J-shaped enlargement

composed of four main regions: the cardia, fundus, body, and pyloric part. As food
may be consumed much faster than the intestines can digest and absorb it, the
stomach serves as a mixing chamber and holding reservoir. Once food ingestion is at
appropriate intervals, the stomach forces a small quantity of material into the first
portion of the small intestine. The stomach forms the chyme, from the mixture of
saliva food and gastric juice. The said gastric juice contains hydrochloric acid, pepsin,
intrinsic factor, and gastric lipase.

→ Small Intestine: This is where most digestion and absorption of nutrients occur. Its
glands secrete fluid and mucus, while the circular folds, villi, and microvilli of its wall
provide a large surface area for digestion and absorption. It is divided into duodenum,
 jejunum, and ileum. It starts at the pyloric sphincter of the stomach, coils through the
central and inferior part of the abdominal cavity, and eventually joins into the large
intestine.

→ Large Intestine: This extends from the ileocecal sphincter up to the anus and is
considered as the terminal portion of the GI tract, estimated to be 1.5 m (5 ft.) long
and 6.5 cm (2.5 in.) in diameter in living humans and cadavers. Its regions include
the cecum, colon, rectum, and anal canal. The large intestine houses many goblet cells
in its mucosa, while having taenia coli and haustra in its muscularis. It absorbs water,
ions and vitamins. The large intestine's overall functions are the completion of
absorption, the production of certain vitamins, the formation of feces, and the
expulsion of feces from the body.

Other than the abovementioned affected organs, the limited cutaneous systemic sclerosis
may also disrupt the function of the lungs, heart, and the musculoskeletal system.

III. Lungs

The lungs are located on either side of the chest (thorax) as a pair of spongy, air-filled
organs. The trachea, also known as windpipe, utilizes tubular branches, called bronchi in
order to conduct inhaled air into the lungs. The bronchi then divide into bronchioles, which
are its smaller branches. At the end lies clusters of microscopic air sacs known as alveoli.
The alveoli have a thin layer of cells called the interstitium, which contains blood vessels
and cells that help support the alveoli. In the alveoli, oxygen from the air is absorbed into
the blood whereas the waste product of metabolism, the carbon dioxide, travels from the
blood to the alveoli for exhaling.

IV. Heart

The heart is about a fist's size, located just posterior and slightly left of the
breastbone. It is surrounded by a sac called the pericardium. Along its surface are
coronary arteries which gives oxygenated blood to the heart muscle. The heart pumps
blood through the network of arteries and veins called the cardiovascular system. This is
controlled by complex signals that control the contraction and relaxation of heart muscles
via a web of nerve tissue that runs through the heart.

The heart has four chambers:

1) The right atrium receives blood from the veins and pumps it to the right ventricle.

2) The right ventricle receives blood from the right atrium and pumps it to the lungs,
loaded with oxygen.

3) The left atrium receives oxygenated blood from the lungs and pumps it to the left
ventricle.

4) The left ventricle (the strongest chamber) pumps oxygen-rich blood to the rest of
the body. The left ventricle’s vigorous contractions create our blood pressure.
 The coronary arteries run along the surface of the heart and provide oxygen-rich blood
to the heart muscle. A web of nerve tissue also runs through the heart, conducting the
complex signals that govern contraction and relaxation. Surrounding the heart is a sac
called the pericardium.

V. Musculoskeletal System

The human body’s movement, stability, shape, and support is provided by the
musculoskeletal system (locomotor system). It is subdivided into two broad systems:

 Muscular system, this involves all types of muscles in the body. Particularly, skeletal
muscles, which act on the body joints to create movements. Besides muscles, it also
includes the tendons, which attach the muscles to the bones.

 Skeletal system, primarily composed of bones, that articulate and form the joints,
providing our bodies with a hard-core yet mobile skeleton. The accessory structures
of the skeletal system such as, articular cartilage, ligaments, and bursae provide the
bones and joints' integrity and function.
C. PATHOPHYSIOLOGY

The pathophysiology of Limited

Cutaneous Systemic Sclerosis or CREST
syndrome revolves around 3 manifestations,
which are collagen deposition, perivascular
mononuclear cell infiltration, and vascular
abnormalities.

Collagen deposition can lead to fibrosis

due to the increase in fibroblast activity. The
collagen type I, III, IV, VII, and proteoglycans,
glycosaminoglycans, and fibronectin are
deposited in the intima and interstitium of
small arteries. The gene that encodes for the alpha-2 chain of type I procollagen, the COL1A2
mRNA, contributes to skin fibroblasts' activation.

Leukocyte recruitment with mononuclear infiltration is considered the first to appear

in pathogenesis since it can manifest with or without fibrosis of the tissue being invaded.
Lymphocytes bearing a CD4 marker are the most concentrated lymphocytes in the
inflammatory infiltrate. The macrophage is also evidently high as these cells secrete
cytokines, which further contributes to fibrosis. One of the cytokines that stimulate collagen
formation is the transforming growth factor-beta (TGF-beta) due to the mRNA produced by
the patient's fibroblast. Also, the pathogenesis of calcinosis is attributed to TGF-beta3. The
high concentration of granulocyte-macrophage colony-stimulating factor (GM-CSF), which is
seen in the patient's serum, contributes to the increased tenascin production fibronectin,
which leads to fibrosis. The inhibitor of collagen synthesis, the interferon-gamma (IFN-
gamma), is produced by the T helper-1. The interleukin 4, which is the promoter synthesis,
is produced by T helper-2; the high concentration of TH2 cell activity contributes to more
collagen synthesis.

Also, the patient's fibroblast with this disease secretes more connective tissue growth
factor (CTGF). It is also reported that their fibroblast does not recognize the tumor necrosis
alpha, which inhibits the activity of CTGF. There is also a marked increase of tissue inhibitor
of metalloproteinase-1 (TIMP-1), which contributes to the fibrosis's progressive state, and
protease nexin 1-gene (PN1) is overstimulated.

Inflammation and endothelial injury lead to vascular abnormalities. The most affected
part is the pericyte, which is a smooth muscle of our vascular system. When there is a disease,
the pericyte density will increase, manifested in the nail fold capillaries attributed to Raynaud's
phenomenon. When there is a problem in our vasculature's normal function, some
consequences may arise but not limited to injury and dysfunction, thrombocytosis, and
vasospasm. Increased platelet-derived growth factor (PDGF) and overexpression of PDGF
type B receptors are also evident, attributed to ischemia.
 Different animal models were used to identify abnormalities, especially in the
scleroderma of humans. The models, such as the tight skin mouse model of scleroderma
(Tsk1) and UCD-200 chicken, an avian model, were used specifically to detect antinuclear
antibody production. The antinuclear antibody production (ANA) is a defect in the fibrillin-1
gene because of the heterozygous mutation.

In short, those aforementioned pathologic features were indicative of CREST

syndrome.
 CHAPTER IV

A. Laboratory Test Results

COMPLETE BLOOD COUNT:

Requested Tests Normal Test Interpretation Rationale

Value Value

Hemoglobin 12.3–15.3 13.3 g/dL WITHIN THE Hemoglobin is a protein moiety in red blood cells that
g/dL NORMAL functions in transporting oxygen from the lungs to the
RANGE different tissues and transporting carbon dioxide from the
tissues back to the lungs.

Hemoglobin estimation indirectly evaluates the oxygen-

carrying capacity of the blood.

The patient's blood is within normal hemoglobin range

despite being diagnosed with scleroderma as this
autoimmune disease affects only the skin, internal organs,
gastrointestinal tract, and blood vessels.

Hematocrit 35.9-44.6 39.9 L/L WITHIN THE Hematocrit is the ratio of packed RBCs that occupies the
L/L NORMAL volume of whole blood.
RANGE
A high or low hematocrit count can indicate clinical
implications depending on both physiologic and pathologic
factors.

The patient's blood is within the normal hematocrit range.

 RBC Count 3.80-5.20 4.4 x WITHIN THE Red Blood Cells (RBCs) are biconcave cells in our blood
x 1012/L 1012/L NORMAL that transports oxygen and carbon dioxide in our body.
RANGE Red Blood Cells are measured in volumes to detect anemia
or polycythemia and in monitoring therapy and treatment.

The patient's blood is within the normal RBC Count range.

WBC Count 3.60-10.60 4.4-11.3 x HIGHER THAN White Blood Cells (WBCs) are cells categorized with
x 109/L 109/L THE NORMAL various cell types that protect our body from infection,
RANGE injury, or trauma.

A high WBC count may be influenced by either physiologic

(stress, anesthesia, and others) or pathologic (infection,
leukemia, and others) factors.

An increase in lymphocytes and eosinophils may increase

the WBC count associated with scleroderma due to an
unknown mechanism of overactivation of these WBC
fractions triggering an autoimmune response.

*Neutrophils 56% 35% LOWER THE Neutrophils are polymorphonuclear cells that phagocytose
NORMAL microorganisms and foreign materials introduced into the
RANGE body.

Neutropenia or low neutrophil levels in scleroderma is

associated with an autoimmune basis.

*Lymphocytes 34% 45% HIGHER THAN Lymphocytes are composed of a complex cellular system
THE NORMAL that functions in host immunity.
RANGE An increase in lymphocytes associated with scleroderma is
due to an unknown mechanism of overactivation. Thus, it
triggers an autoimmune response due to release of
cytokines.
*Eosinophils 2.7% 4% SLIGHTLY Eosinophils are granular cells with proteins involved in
HIGHER THAN immune system regulation. An increase in these cells
THE NORMAL indicates a response to allergy or parasitic infection.
RANGE
Increased eosinophil in people associated with
scleroderma is due to an increase in cytokines. Thus, the
overactivation of these specific white blood cells.

*Basophils 0.3% 1% SLIGHTLY Basophils are granular cells that contain histamines and
HIGHER THAN other proteins that function in the immune response. The
THE NORMAL distribution of these cells in the blood usually is low, and
RANGE an increase in these cells is also rare.

The patient's basophil fraction in white blood cells is

slightly higher than the normal range. In scleroderma,
there is no associated increase in basophil. A level of 1%
basophil is still in a normal range and is not that elevated.

*Monocytes 4% 15% SLIGHTLY Monocytes are immature macrophages that have the same
HIGHER THAN function as neutrophils in the phagocytosis of foreign
THE NORMAL materials. They also assist the lymphocytes during
RANGE immune responses.

Increased monocyte levels are generally observed in

autoimmune diseases such as scleroderma due to its
infiltration into the skin.

Platelets 150-450 152 x WITHIN THE Platelets are blood cells that maintain blood vessels'
x 109/L 109/L NORMAL integrity by initiating blood vessel wall repairs.
RANGE
The patient's platelet count is within the normal range.
ESR <30 35 mm/hr HIGHER THAN Erythrocyte Sedimentation Rate is a nonspecific test used
mm/hr THE NORMAL to detect inflammation. It can be used to monitor
RANGE inflammatory conditions or diseases and certain
malignancies.

Elevated ESR is a common feature of patients with

scleroderma. It is also an inflammatory marker in
assessing disease activity in scleroderma.
SERUM CHEMISTRY PANEL:

Requested Tests Normal Test Interpretation Rationale

Value Value

FBS 3.9–6.1 4.5 WITHIN THE Fasting Blood Sugar or Fasting Plasma Glucose is a
mmol/L mmol/L NORMAL specimen collected after 8-10 hours of fasting. It is also
RANGE used to assess the body's ability to manage blood sugar
levels in the absence of food and diagnose diabetes.

The patient's Fasting Blood Sugar is within the normal

range as scleroderma only affects the skin, internal
organs, gastrointestinal tract, and blood vessels.
Some studies suggest that patients diagnosed with
scleroderma coexist with diabetes.

Scleroderma can also cause a Type B insulin resistance

syndrome.

SUA 160–430 375 WITHIN THE Serum Uric Acid is the product of the catabolism of purines
µmol/L µmol/L NORMAL in nucleic acids. At higher concentrations, it can be
RANGE deposited in the joints and tissues, thus causing
inflammation. It is also used to diagnose and confirm gout.

The patient's Serum Uric Acid is within the normal range.

In some studies, increased serum uric acid can be a
marker for people diagnosed with Pulmonary Arterial
Hypertension in scleroderma, specifically in Diffuse
Cutaneous Systemic Sclerosis.

Creatinine 0.6–1.2 0.88 WITHIN THE Creatinine is a non-protein nitrogenous compound that is
mg/dL mg/dL NORMAL excreted into the plasma at a constant rate. It is also used
RANGE to assess Glomerular Filtration Rate (GFR) or simply the
kidneys' function.
 The creatinine level of the patient is within the normal
range. Thus, the function of the kidneys is normal. Urine
Tests are often normal in people diagnosed with Limited
Cutaneous Systemic Sclerosis.

SGPT 4-36 U/L 41 U/L HIGHER THAN Serum Glutamic-Pyruvic Transaminase is a transferase
THE NORMAL that is a liver-specific enzyme. It is used to evaluate
RANGE hepatic disorders.

The Serum Glutamic-Pyruvic Transaminase level of the

patient is higher than the normal range. In some cases,
liver enzyme tests like SGPT are elevated in scleroderma
as some hepatic manifestations are reported with this
disease.

HbA1C <5.7% 4.7 % WITHIN THE HbA1C or Glycosylated Hemoglobin is the formation of a
NORMAL hemoglobin compound linked with glucose in its amino
RANGE group. It is a reliable method in monitoring long-term
diabetes.

The patient's Fasting Blood Sugar is within the normal

range. Also, scleroderma can cause a Type B insulin
resistance syndrome.
SEROLOGICAL TESTS:

Requested Tests Normal Test Interpretation Rationale

Value Value

Rheumatoid <20 IU/mL 11 IU/mL WITHIN THE Rheumatoid Factor is an antibody, usually of IgM class,
Factor NORMAL that is directed against the Fc portion of the IgG.
RANGE Rheumatoid Factor is not specific for Rheumatoid Arthritis
as it can also be detected with other autoimmune diseases
involving connective tissues such as Systemic Lupus
Erythematosus and Scleroderma.

It can also be seen in normal individuals or other unrelated

joint diseases. In the patient's case, her Rheumatoid
Factor levels in the blood are within the normal range.
Despite this, she is still positive for Rheumatoid Factor,
which is detectable with autoimmune diseases such as
scleroderma.

ANA (Qualitative) Negative Centromer ABNORMAL Antinuclear Antibodies (ANAs) are heterogenous
e pattern autoantibodies that react against the whole nucleus or its
nuclear components (DNA, centromere, histones, non-
histone proteins, and nucleolar antigens) of host tissue. It
is also not specific for Systemic Lupus Erythematosus.

One of the systematic classifications of Antinuclear

Antibodies are antibodies specific to the centromeres. In
the patient's case, her Antinuclear Antibodies are in a
centromere pattern or are directed against the
centromere. In 50-80% of patients with Limited
Cutaneous Systemic Sclerosis (more commonly known as
CREST syndrome), anticentromere antibodies are found.
CRP 0.47-1.34 5.9 mg/L HIGHER THAN C-Reactive Protein (CRP) is a member of the pentraxin
mg/L THE NORMAL family and is one of the acute phase reactants. They
RANGE appear in the plasma during many infectious or
inflammatory conditions.

CRPs are also used clinically to monitor autoimmune

diseases and as a risk marker for cardiovascular diseases.

In the patient's case, she has an elevated CRP level in the

blood. Although most people diagnosed with scleroderma
have a normal and stable CRP level, CRP level is elevated
in one‐quarter of scleroderma patients.
URINALYSIS:

Requested Tests Normal Test Interpretation Rationale

Value Value

Color Pale Yellow Light NORMAL The yellow color of urine is mainly due to pigment
to Deep yellow urochrome, a derivative of urobilin. The excretion of this
Amber pigment is proportional to the metabolic rate of a person.
Pale yellow urine typically indicates low specific gravity
and is excreted following a high fluid intake.

The patient has normal urine color even though diagnosed

with scleroderma. It is because renal involvement is rare
in patients with Limited Cutaneous Systemic Sclerosis as
in with the patient.

Transparency Clear Hazy ABNORMAL A differential diagnosis of hazy or cloudy urine is broad,
and it may include several non-pathologic conditions.
Cloudy or hazy urine can also be attributed to various
cellular elements such as leukocytes, erythrocytes,
epithelial cells, and spermatozoa.

The patient has hazy or cloudy urine, even though renal

involvement is rare in Limited Cutaneous Systemic
Sclerosis. There are such reported cases wherein the
people diagnosed with Limited Cutaneous Systemic
Sclerosis have turbid urine but normal renal function.

Protein Negative Trace SLIGHTLY Typically, the average protein concentration in urine varies
ABNORMAL from 2 to 10 mg/dL, dependent on urine volume.
Detection of an abnormal amount of protein in the urine is
an indicator of renal disease.
 In the case of the patient, there is a trace amount of
protein in her urine. Most people diagnosed with
scleroderma exhibit proteinuria but are less likely to be in
higher concentrations but only in trace amounts.

Glucose Negative Negative NORMAL Glucose may appear in the urine at various blood glucose
levels, and it is not always associated with hyperglycemia.

The patient has a negative amount of glucose in her urine.

This negative amount of glucose in the urine is associated
with rare renal involvement in patients with Limited
Cutaneous Systemic Sclerosis.

pH 4.6-8.0 6.0 WITHIN THE Due to the Na+/H+ exchange pump mechanism of the
NORMAL renal tubules, the pH increases as sodium is retained.
RANGE
The patient's pH is within the normal range of value as,
again, there is a rare renal involvement in patients with
Limited Cutaneous Systemic Sclerosis.

Specific Gravity 1.003 to 1.015 WITHIN THE Specific gravity indicates the density of urine dependent
1.035 NORMAL on its concentration of total dissolved solids. It is also used
RANGE to assess the hydration or dehydration status and indicate
an individual's urine concentration.

The patient's specific gravity is within the normal range

because, as mentioned, renal involvement is rare in
patients with Limited Cutaneous Systemic Sclerosis.

Pus cells 0-1/hpf 1-3/hpf HIGHER THAN Pyuria is the increase in the number of White Blood Cells
THE NORMAL or Pus Cells in the urine greater than 0-1/hpf. It is
RANGE observed when there is acute glomerulonephritis, urinary
tract infection, or inflammation of any type.

In the patient's case, pyuria is observed as the number of

pus cells in her urine is higher than the normal range
indicated by inflammation.
 RBC 0-2/hpf 2-4/hpf HIGHER THAN Gross Hematuria is an increased number of Red Blood
THE NORMAL Cells (0-2/hpf) in the urine (10). It is considered abnormal
RANGE if test values are greater than the specified normal range,
just like in the patient's case diagnosed with scleroderma.

Urinalysis demonstrates mild proteinuria and hematuria in

5-10% of patients diagnosed with scleroderma.

Mucus threads Negative (+) POSITIVE Mucus is a thick and slimy substance that coats and
(-) moisten various parts of the body, including the nose,
mouth, throat, and urinary tract.

In the patient's case, urinalysis revealed that her urine is

positive for mucus threads, which is a small amount is
normal.

Epithelial cells 0-2/hpf or (+) POSITIVE Several epithelial cells are frequently present in normal
Negative urine because they are continuously sloughed off the lining
(-) of the nephrons and urinary tract.

Female patients usually exhibit large, flat, squamous

vaginal epithelia in their urine, as in the case with the
patient.
B. Medication Used and Their Actions

The patient was not given any medication upon the onset of her medical and laboratory
evaluations. However, patient history revealed that she was under a proton-pump inhibitor
therapy to improve gastrointestinal symptoms as she experienced esophageal dysmotility.
Proton-pump inhibitors (PPI) are classes of medications that block and reduce stomach
acid production. PPIs are mostly a common therapy given to those patients who
experience GERD (Gastroesophageal Reflux Disease). Also, PPIs give any damaged
esophageal tissue time to heal. PPIs are usually prescribed to those patients diagnosed
with scleroderma, as in the case of the patient. This is because the risk of permanent
damage with gastroesophageal reflux will outweigh the medications' possible long-term
side effects.
 CHAPTER V

A. Summary

This 52-year-old female patient had a 15-year history of Raynaud's

phenomenon, preceding the onset of other symptoms. Upon the performance of
laboratory evaluation, it was presented that the patient is having esophageal
dysmotility, sclerodactyly, and calcinosis, which are features of Limited Cutaneous
Systemic Sclerosis or previously known as CREST Syndrome.

Serological tests were performed and having a centromere pattern in an

antinuclear antibody implies a better prognosis.

B. Conclusion

The patient was positive for an antinuclear antibody. That fact is very evident
in this case due to the centromere pattern. The challenge is to differentiate whether
or not the case is a limited cutaneous or diffuse cutaneous involvement. The symptoms
present in the patient allows the examiner to confirm a limited cutaneous type of
sclerosis.

Laboratory scientists should perform laboratory tests with an extra precaution,

and the clinician should have a trained clinical eye for proper diagnosis of the disease
and apply proper treatment.

C. Recommendation

Based on the findings and conclusion of this case study, the following
recommendations are proposed:

1. Appropriate clinical tests must be performed in order to assess the health situation
of the patient fully. Thus, clinical and laboratory findings are needed in the
diagnosis.

2. Refer patients positive with antinuclear antibody to a rheumatologist.

3. There is still no cure for scleroderma, but it is highly recommended to focus on

treating or relieving the symptoms (CREST) by medical management such as;
Proton-Pump Inhibitor Therapy should be continued to manage the
gastroesophageal reflux; Calcium Channel Blockers in episodes of Raynaud’s
phenomenon; Non-steroid Anti-Inflammatory Drugs for tendon and joint pains;
Steroid creams or pills to help reduce swelling and joint pain and to loosen stiff
skin; and stronger Immunosuppressants to help slow down the immune reaction
of the disease.

4. Physical therapy hand exercises are prescribed.

5. Annual assessments should be conducted, including pulmonary function tests, to
measure how well the lungs are functioning and an echocardiogram to monitor the
heart.

6. A healthy and balanced diet, exercising regularly, and a good skincare routine are
also important.

7. The patient should also wear warm clothes during cold weather, especially on the
hands and feet, to prevent Raynaud’s phenomenon.

8. The patient and the people close to them must be informed about the disease to
prevent any consequences that can trigger it.

9. Proper diagnosis is essential since early ascertainment of internal organ

involvement leads to better outcomes.
 CHAPTER VI

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