Leprosy

Overview

Definition

Leprosy (also known as Hansen’s disease) is an infectious disease affecting skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions and peripheral nerves Peripheral Nerves The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. Nervous System: Histology.

Epidemiology

• Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency: < 1 in 10,000 since 2002
• Highest incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in India, Brazil, Indonesia, Bangladesh, and Nigeria
• In 2015, there were 178 new cases of leprosy in the United States. 
• Immigrants account for 75% of new cases in the United States.

Etiology

Leprosy is caused by Mycobacterium leprae Mycobacterium leprae A species of gram-positive, aerobic bacteria that causes leprosy in man. Its organisms are generally arranged in clumps, rounded masses, or in groups of bacilli side by side. Mycobacterium complex bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology:

• Includes M. leprae and M. lepromatosis
• Acid-fast bacilli Acid-fast bacilli Mycobacterium 
• Aerobic, obligate intracellular rod-shaped bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology

Risk factors for acquisition:

• Close contact with leprosy patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
• Exposure to 9-banded armadillos (natural reservoir Reservoir Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (disease vectors) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks. Humans may serve both as disease reservoirs and carriers. Escherichia coli of M. leprae in the southern U.S.)
• Older age
• Genetic factors
• Immunosuppression

Pathophysiology

• Bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology are inhaled or transmitted through direct skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions contact and are taken up by alveolar macrophages Alveolar macrophages Round, granular, mononuclear phagocytes found in the alveoli of the lungs. They ingest small inhaled particles resulting in degradation and presentation of the antigen to immunocompetent cells. Acute Respiratory Distress Syndrome (ARDS) and disseminated in the blood. 
• M. leprae spreads to nerves and skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions, where it proliferates (especially in Schwann cells).
• Leprosy can manifest in different forms that reflect a spectrum of the host immune response.
• Ridley–Jopling classification of leprosy:
  • Tuberculoid (TT)
  • Borderline tuberculoid (BT)
  • Mid-borderline (BB)
  • Borderline lepromatous (BL)
  • Lepromatous (LL)
  • Indeterminate (I)
• Tuberculoid and lepromatous forms are at the 2 ends of the spectrum:
  • Tuberculoid leprosy Tuberculoid Leprosy Antimycobacterial Drugs:
    • Good cellular immune response ( type 1 Type 1 Spinal Muscular Atrophy T helper ( TH1 Th1 A subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2; interferon-gamma; and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, th1 cells are associated with vigorous delayed-type hypersensitivity reactions. T cells: Types and Functions) cell response)
    • Delayed-type hypersensitivity Delayed-type hypersensitivity Type IV hypersensitivity reaction, or delayed-type hypersensitivity, is a cell-mediated response to antigen exposure. The reaction involves T cells, not antibodies, and develops over several days. Presensitized T cells initiate the immune defense, leading to tissue damage. Type IV Hypersensitivity Reaction with interferon-γ and macrophage activation Macrophage activation The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (maf) and the macrophage migration-inhibitory factor (mmif), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants. IL-12 Receptor Deficiency
    • Involves the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions (localized) and peripheral nerves Peripheral Nerves The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. Nervous System: Histology
  • Lepromatous leprosy Lepromatous Leprosy Antimycobacterial Drugs:
    • Minimal cellular immune response
    • Humoral (antibody) response (activated by type 2 T helper ( TH2 Th2 A subset of helper-inducer T-lymphocytes which synthesize and secrete the interleukins il-4; il-5; il-6; and il-10. These cytokines influence b-cell development and antibody production as well as augmenting humoral responses. T cells: Types and Functions) cells)
    • Extensive skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions involvement
    • Nerve involvement tends to be symmetric.

Clinical Presentation

Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions lesions:

• Well demarcated in tuberculoid leprosy Tuberculoid Leprosy Antimycobacterial Drugs:
  • Usually 1 or 2 lesions
  • Central hypopigmentation Hypopigmentation A condition caused by a deficiency or a loss of melanin pigmentation in the epidermis, also known as hypomelanosis. Hypopigmentation can be localized or generalized, and may result from genetic defects, trauma, inflammation, or infections. Malassezia Fungi or erythematous
  • Hypoesthesia
• Poorly demarcated in lepromatous leprosy Lepromatous Leprosy Antimycobacterial Drugs:
  • Can be macular, raised, or nodular
  • Numerous; appear all over body

Other manifestations:

• Neuropathy, paresthesias Paresthesias Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. Posterior Cord Syndrome
• Enlarged and tender peripheral nerves Peripheral Nerves The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. Nervous System: Histology ( tuberculoid leprosy Tuberculoid Leprosy Antimycobacterial Drugs)
• Painless extremity wounds
• Facial or ear lumps
• Ophthalmic injury:
  • Lagophthalmos (inability to close eyelids Eyelids Each of the upper and lower folds of skin which cover the eye when closed. Blepharitis completely)
  • Corneal abrasions Abrasions Corneal Abrasions, Erosion, and Ulcers/ulcerations

Late findings may include:

• Facial paralysis
• Collapsed nose Nose The nose is the human body’s primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Nose Anatomy (External & Internal)
• Clawed fingers
• Foot Foot The foot is the terminal portion of the lower limb, whose primary function is to bear weight and facilitate locomotion. The foot comprises 26 bones, including the tarsal bones, metatarsal bones, and phalanges. The bones of the foot form longitudinal and transverse arches and are supported by various muscles, ligaments, and tendons. Foot: Anatomy drop
• Lack of eyelashes/eyebrows

Possible immunologic reactions:

• Systemic inflammatory complications
• May occur before, during, or after treatment
• Two types:
  • Type 1 Type 1 Spinal Muscular Atrophy: reversal reaction
  • Type 2: erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion nodosum leprosum
• Can be difficult to distinguish clinically
• Symptoms include:
  • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, malaise Malaise Tick-borne Encephalitis Virus
  • Neuritis, arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis, iritis, nasopharyngeal symptoms

Lucio’s phenomenon:

• Very rare complication of lepromatous leprosy Lepromatous Leprosy Antimycobacterial Drugs
• Necrotizing vasculopathy

Diagnosis

World Health Organization (WHO) diagnostic criteria

The WHO defines leprosy as appearing in an individual who has not completed a course of treatment and has one or more of the following:

• Painless hypopigmented or reddish skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions lesions
• Peripheral nerve thickening and associated loss of sensation
• Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions smear positive for acid-fast bacilli Acid-fast bacilli Mycobacterium

The WHO bases Bases Usually a hydroxide of lithium, sodium, potassium, rubidium or cesium, but also the carbonates of these metals, ammonia, and the amines. Acid-Base Balance diagnosis on the above clinical presentation combined with a confirmatory laboratory test.

Laboratory studies

• Skin biopsy Skin Biopsy Secondary Skin Lesions:
  • Full-thickness sample taken from most active margin of most active lesion
  • The Ziehl–Neelsen or Fite stain can show the presence of acid-fast bacilli Acid-fast bacilli Mycobacterium, confirming the diagnosis of leprosy.
  • Slit-skin smear can help in diagnosing those with lepromatous disease.
  • M. leprae cannot be cultured in artificial media.
  • Mycobacterial culture may need to be performed to rule out other pathogens (M. tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis).
• Serologic assays:
  • Detect phenolic-glycolipid-1 and lipoarabinomannan
  • 95% sensitivity for lepromatous leprosy Lepromatous Leprosy Antimycobacterial Drugs 
  • 30% sensitivity for tuberculoid leprosy Tuberculoid Leprosy Antimycobacterial Drugs
• Molecular probes:
  • Detect 40%–50% of cases missed on histologic evaluation
  • Can fail to identify tuberculoid leprosy Tuberculoid Leprosy Antimycobacterial Drugs
• PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR):
  • Gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics probes with M. leprae–specific sequences
  • Can be used to identify mycobacterium Mycobacterium Mycobacterium is a genus of the family Mycobacteriaceae in the phylum Actinobacteria. Mycobacteria comprise more than 150 species of facultative intracellular bacilli that are mostly obligate aerobes. Mycobacteria are responsible for multiple human infections including serious diseases, such as tuberculosis (M. tuberculosis), leprosy (M. leprae), and M. avium complex infections. Mycobacterium in biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma samples, skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions, nasal smears, blood, and tissue sections
• Lymphocyte migration inhibition test:
  • Tests for cell-mediated immunity Cell-mediated immunity Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role. Squamous Cell Carcinoma (SCC) to M. leprae
  • Absent in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with lepromatous leprosy Lepromatous Leprosy Antimycobacterial Drugs
  • Present in those with tuberculoid leprosy Tuberculoid Leprosy Antimycobacterial Drugs
• Lepromin test:
  • Not available in the United States
  • Test is done by injecting antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination intradermally.
  • Check the injection site for induration Induration Dermatologic Examination, similar to what is done for the tuberculin Tuberculin A protein extracted from boiled culture of tubercle bacilli (Mycobacterium tuberculosis). It is used in the tuberculin skin test (tuberculin test) for the diagnosis of tuberculosis infection in asymptomatic persons. Type IV Hypersensitivity Reaction skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions test.
  • Not reliable: detects ability to develop granulomas Granulomas A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. Sarcoidosis when exposed to antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination but not the actual exposure

Management

Management

• Multidrug therapy (MDT) regimen:
  • Necessary to prevent drug resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing
  • Dapsone Dapsone A sulfone active against a wide range of bacteria but mainly employed for its actions against Mycobacterium leprae. Its mechanism of action is probably similar to that of the sulfonamides which involves inhibition of folic acid synthesis in susceptible organisms. It is also used with pyrimethamine in the treatment of malaria. Antimycobacterial Drugs + rifampin Rifampin A semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. Epiglottitis + clofazimine Clofazimine A fat-soluble riminophenazine dye used for the treatment of leprosy. It has been used investigationally in combination with other antimycobacterial drugs to treat Mycobacterium avium infections in AIDS patients. Clofazimine also has a marked anti-inflammatory effect and is given to control the leprosy reaction, erythema nodosum leprosum. Antimycobacterial Drugs for 6 months for Tuberculoid (TT) and Borderline tuberculoid (BT) leprosy
  • Dapsone Dapsone A sulfone active against a wide range of bacteria but mainly employed for its actions against Mycobacterium leprae. Its mechanism of action is probably similar to that of the sulfonamides which involves inhibition of folic acid synthesis in susceptible organisms. It is also used with pyrimethamine in the treatment of malaria. Antimycobacterial Drugs + rifampin Rifampin A semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. Epiglottitis + clofazimine Clofazimine A fat-soluble riminophenazine dye used for the treatment of leprosy. It has been used investigationally in combination with other antimycobacterial drugs to treat Mycobacterium avium infections in AIDS patients. Clofazimine also has a marked anti-inflammatory effect and is given to control the leprosy reaction, erythema nodosum leprosum. Antimycobacterial Drugs for 12 months for Borderline lepromatous (BL), Lepromatous (LL), and Mid-borderline (BB) leprosy
  • Alternative medications:
    • Minocycline Minocycline A tetracycline analog, having a 7-dimethylamino and lacking the 5 methyl and hydroxyl groups, which is effective against tetracycline-resistant staphylococcus infections. Tetracyclines
    • Ofloxacin Ofloxacin A synthetic fluoroquinolone antibacterial agent that inhibits the supercoiling activity of bacterial DNA gyrase, halting DNA replication. Fluoroquinolones
    • Levofloxacin Levofloxacin The l-isomer of ofloxacin. Fluoroquinolones
    • Clarithromycin Clarithromycin A semisynthetic macrolide antibiotic derived from erythromycin that is active against a variety of microorganisms. It can inhibit protein synthesis in bacteria by reversibly binding to the 50s ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. Macrolides and Ketolides
    • Moxifloxacin Moxifloxacin A fluoroquinolone that acts as an inhibitor of DNA topoisomerase II and is used as a broad-spectrum antibacterial agent. Fluoroquinolones
• Immunologic reactions:
  • Can be managed supportively if mild and no neuritis is present
  • Neuritis must be managed aggressively to prevent permanent nerve damage.
  • Steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors and immunosuppressants Immunosuppressants Immunosuppressants are a class of drugs widely used in the management of autoimmune conditions and organ transplant rejection. The general effect is dampening of the immune response. Immunosuppressants

Prevention

• No drug prophylaxis Prophylaxis Cephalosporins in nonendemic areas
• BCG BCG An active immunizing agent and a viable avirulent attenuated strain of Mycobacterium bovis, which confers immunity to mycobacterial infections. It is used also in immunotherapy of neoplasms due to its stimulation of antibodies and non-specific immunity. Cancer Immunotherapy vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination is partly protective.
• Close contacts of affected individuals:
  • Should be monitored annually for at least 5 years.
  • Single-dose rifamycin for close contacts of lepromatous leprosy Lepromatous Leprosy Antimycobacterial Drugs patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with high bacterial load
  • WHO and China recommend rifapentine Rifapentine Antimycobacterial Drugs or rifampin Rifampin A semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. Epiglottitis prophylaxis Prophylaxis Cephalosporins for contacts.

Complications

• Paralysis and crippling of hands and feet
• Autoamputation of toes and fingers
• Chronic nonhealing ulcers on bottoms of feet
• Blindness Blindness The inability to see or the loss or absence of perception of visual stimuli. This condition may be the result of eye diseases; optic nerve diseases; optic chiasm diseases; or brain diseases affecting the visual pathways or occipital lobe. Retinopathy of Prematurity
• Loss of eyebrows
• Nose Nose The nose is the human body’s primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Nose Anatomy (External & Internal) disfigurement
• Testicular atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation

Differential Diagnosis

• Neurofibromatosis type 1 Type 1 Spinal Muscular Atrophy: a genetic neural disorder of benign Benign Fibroadenoma tumors that arise from the neural crest cells Neural crest cells Gastrulation and Neurulation in the peripheral nerve sheath: Neurofibromatosis type 1 Type 1 Spinal Muscular Atrophy presents in the teen years as soft, painless skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions nodules. Genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies can confirm the diagnosis after the physical exam and biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. Management includes surgical resection and antitumor drugs. 
• Dermatofibroma (DF): a common, benign Benign Fibroadenoma, fibrohistiocytic proliferation reaction, usually in reaction to trauma, a viral infection, or an insect bite: Dermatofibroma presents on the anterior surfaces of the lower legs as a firm, indurated, mobile nodule Nodule Chalazion that retracts beneath the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions during an attempt to compress and elevate it. Diagnosis is by biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. Management includes surgical resection. 
• Systemic lupus erythematosus: a systemic autoimmune disorder most commonly affecting women: Patients can present with involvement of multiple organs. Cutaneous manifestations of lupus include facial “butterfly rash” or generalized erythematous macular–papular eruption involving sun-exposed areas. Diagnosis is based on clinical suspicion and the presence of certain antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions. Management involves steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors, immunosuppressants Immunosuppressants Immunosuppressants are a class of drugs widely used in the management of autoimmune conditions and organ transplant rejection. The general effect is dampening of the immune response. Immunosuppressants, and biologic agents Biologic Agents Immunosuppressants.
• Scleroderma Scleroderma Scleroderma (systemic sclerosis) is an autoimmune condition characterized by diffuse collagen deposition and fibrosis. The clinical presentation varies from limited skin involvement to diffuse involvement of internal organs. Scleroderma: an autoimmune condition characterized by diffuse collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology deposition and fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans: The clinical presentation varies from limited skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions involvement to diffuse involvement of internal organs. Diagnosis is established by a combination of physical findings and serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus. There is no curative treatment. Management options are limited but include immunosuppressive medications and symptomatic treatment.