INTRODUCTION — Lymphangitis is inflammation of lymphatic channels due to infectious or noninfectious causes. Potential pathogens include bacteria, mycobacteria, viruses, fungi, and parasites. Lymphangitis most commonly develops after cutaneous inoculation of microorganisms into the lymphatic vessels through a skin wound or as a complication of a distal infection.
The pathophysiology, clinical manifestations, microbiology, diagnosis, and treatment of lymphangitis will be reviewed here. Further information about the individual etiologies of lymphangitis is discussed in detail separately.
PATHOPHYSIOLOGY — The major function of the lymphatic system is to resorb fluid and protein from tissues and extravascular spaces. The absence of a basement membrane beneath lymphatic endothelial cells affords the lymphatic channels a unique permeability, allowing resorption of proteins that are too large to be resorbed by venules.
Lymphatic channels are situated in the deep dermis and subdermal tissues parallel to the veins and have a series of valves to ensure one-way flow [1]. Lymph drains via afferent lymphatics to regional lymph nodes and then by efferent lymphatics to the cisterna chyli and the thoracic duct into the subclavian vein and venous circulation.
Lymphangitis most commonly develops after cutaneous inoculation of microorganisms that invade the lymphatic vessels and spread toward the regional lymph nodes. Organisms may invade lymphatic vessels directly through a skin wound or an abrasion or as a complication of a distal infection.
Lymphangitis can occur in the setting of:
●Normal lymphatic channels with acute infection – A virulent infecting organism (such as Streptococcus pyogenes) gains entry to lymphatic channels through a distal skin breach or disruption from local trauma or dermatophyte infection.
●Damaged lymphatic channels – Damage to lymphatic channels with obstruction can occur in the setting of surgical procedures, malignancy, radiation, and trauma. In the lower limbs, for example, saphenous vein harvesting for coronary artery bypass surgery can result in damage to and obstruction of lymphatic channels. The same is true in the upper limbs in the setting of radical mastectomy including dissection with removal of axillary lymph nodes [2]. (See "Early noncardiac complications of coronary artery bypass graft surgery", section on 'Post-venectomy cellulitis' and "Cellulitis following pelvic lymph node dissection".)
●Anatomic abnormalities – Congenital or developmental defects resulting in hypoplastic or hyperplastic changes can result in obstruction of lymphatic channels with complicating secondary lymphangitis. (See "Pathophysiology and etiology of edema in children", section on 'Primary lymphedema'.)
Lymphatic damage and anatomic abnormalities can result in tissue protein and fluid accumulation, leading to nonpitting lymphedema with induration and predisposing to invasion of microorganisms.
CLINICAL MANIFESTATIONS AND MICROBIOLOGY — Lymphangitis has a spectrum of clinical presentations and etiologies. The clinical manifestations of lymphangitis are variable and may be characterized by erythematous streaks with pain and rapid spread or by nodular swellings along the course of the lymphatic vessels. Lymphangitis can also occur as a complication of an infected peripheral intravenous catheter [3]. A detailed clinical history including epidemiology of occupational or recreational exposure should be combined with careful clinical assessment and collection of targeted clinical specimens.
Acute lymphangitis — Acute lymphangitis may occur in the setting of skin abrasion with infection at a distal site, such as interdigital dermatophyte infection or cellulitis or erysipelas of the lower leg. This may be accompanied by lymphangitis with red, tender streaks extending proximally with involvement of regional lymph nodes (lymphadenitis). Acute lymphangitis often occurs in the setting of systemic symptoms including fever.
In individuals with normal immunity, the most common causative organism is S. pyogenes; lymphangitis can also occur in the setting of Staphylococcus aureus infection. In immunocompromised patients, gram-negative organisms are also important causes of lymphangitis following lower limb cellulitis.
Pasteurella multocida (from cat, dog, or other animal bite) and B. henselae infection (following a cat bite) can result in localized infection with concomitant lymphangitis [4]. Lymphangitis also occurs in up to 30 percent of Erysipelothrix infections, a zoonosis occurring in persons in contact with fish and some animals. Cutaneous anthrax can present with extensive edema, regional lymphadenopathy, and lymphangitis [5]. Occupational milker's nodule caused by parapoxvirus may present with lymphangitis [6]. (See "Erysipelothrix infection" and "Clinical manifestations and diagnosis of anthrax" and "Pasteurella infections" and "Zoonoses: Animals other than dogs and cats" and "Zoonoses: Animals other than dogs and cats", section on 'Deer, sheep, cattle, goats, and camels'.)
Lymphangitis has been reported as an uncommon manifestation of herpes simplex virus ("whitlow") [7] in the setting of limb or genital infection [8]. Lymphogranuloma venereum spreads from the primary site of infection to the draining lymph nodes and may produce a local lymphangitis [9,10]. (See "Lymphogranuloma venereum".)
Lymphangitis associated rickettsiosis has been described with the causative organism Rickettsia sibirica mongolotimonae and in African tick bite fever due to Rickettsia africae [11-13]. The presence of an inoculation eschar suggests tick-transmitted infection. (See "Other spotted fever group rickettsial infections".)
Spider bites complicated by infection with lymphangitis have also been described [14].
Nodular lymphangitis — Nodular lymphangitis (also known as sporotrichoid lymphangitis, sporotrichoid spread, or lymphocutaneous syndrome) presents as painful or painless nodular subcutaneous swellings along the course of the lymphatic channels [15,16]. Some of the lesions may ulcerate with accompanying regional lymphadenopathy. The incubation period between exposure and the onset of nodular lymphangitis can be prolonged, and the presentation may be indolent with few or no systemic symptoms.
The epidemiology and appearance of the lesion may point to a specific etiology. Causes of nodular lymphangitis include Sporothrix schenckii, Nocardia (most often N. brasiliensis), Mycobacterium marinum, leishmaniasis, tularemia, and systemic mycoses [15,17-19].
●Sporotrichosis has been described in the setting of gardening trauma or injury due to a thorn or wood splinter [15]. It can have an incubation period of up to three months and presents in a cutaneous or a lymphocutaneous form accompanied by lymphangitis; painless ulcers may also be observed. Lesions on the upper limbs are the most common presentation [16,17]. (See "Clinical features and diagnosis of sporotrichosis".)
●M. marinum has been described to cause "fish tank granuloma" (also called "swimming pool granuloma"), an entity that can occur following a hand injury while cleaning a fish tank. It has an incubation period of up to eight weeks [15,16]. Infection due to rapidly growing mycobacteria can also occur in the setting of thorn or splinter injury. Other mycobacterial causes of lymphangitis include Mycobacterium kansasii, Mycobacterium chelonae, and Mycobacterium fortuitum. (See "Soft tissue infections following water exposure".)
●Nocardia infections may present with cutaneous, subcutaneous, or lymphocutaneous manifestations following traumatic injury. Although this may mimic the appearance and clinical course of acute staphylococcal or streptococcal infection, the clinical course is usually much more indolent [18]. Many Nocardia species have been described as causing nodular lymphangitis [20-22]. (See "Clinical manifestations and diagnosis of nocardiosis".)
●Cutaneous leishmaniasis can present with subcutaneous nodules with lymphangitis or lymphadenitis up to 24 weeks following exposure [16]. This presentation is more frequent with New World leishmaniasis caused by Leishmania braziliensis or Leishmania mexicana than with Old World leishmaniasis due to Leishmania major or Leishmania tropica [15]. (See "Cutaneous leishmaniasis: Clinical manifestations and diagnosis".)
●Nodular lymphangitis is a rare manifestation of Francisella tularensis and Burkholderia pseudomallei infection [16,23]. The initial skin lesion of F. tularensis infection may be a papule or an ulcer or contain an eschar. Similarly, Scedosporium apiospermum can cause lymphocutaneous infection, especially in immunocompromised host [24]. (See "Tularemia: Clinical manifestations, diagnosis, treatment, and prevention" and "Melioidosis: Epidemiology, clinical manifestations, and diagnosis".)
●The systemic mycoses, including coccidioidomycosis, blastomycosis, and histoplasmosis, can present with nodular lymphangitis. This most commonly results from hematogenous dissemination, although primary skin inoculation followed by sporotrichoid spread has also been described [15,16].
The nature of a distal primary lesion may aid the diagnosis. Painless ulcers may be observed in S. schenckii, leishmania (with or without satellite lesions), and F. tularensis infection, while tender lesions may due to Nocardia or M. marinum [16]. However, initial lesions may manifest in a variety of forms, and the primary lesion may have healed prior to presentation. In this setting, a patient may present with localized proximal lymphadenopathy rather than the more peripheral lesions. The evaluation and management of peripheral lymphadenopathy are discussed separately. (See "Evaluation of peripheral lymphadenopathy in adults" and "Peripheral lymphadenopathy in children: Evaluation and diagnostic approach" and "Peripheral lymphadenopathy in children: Etiology".)
In general, the microbiologic diagnosis of nodular lymphangitis generally requires aspiration or biopsy of a nodule for microscopy and culture. (See 'Diagnosis' below.)
Filarial lymphangitis — Lymphangitis due to filariasis has distinctive clinical manifestations. The presence of the parasite within the lymphatic channels causes inflammation and subsequent dilatation, thickening, and tortuosity of the lymphatic channels with valvular incompetence. Filarial lymphangitis often occurs in a retrograde progression with distal or peripheral spread away from the regional lymph nodes where the adult parasite resides. Lymphangitis can also occur as a result of inflammation due to dying parasites. Subsequent lymphedema with thickening of skin and subcutaneous tissue can predispose to repeated episodes secondary bacterial infection [25,26].
Wuchereria bancrofti, Brugia malayi, and Brugia timori are the causes of lymphangitis due to lymphatic filariasis. Filarial lymphangitis is uncommon in short-term travelers but may be considered in individuals who have spent prolonged periods in endemic areas. (See "Lymphatic filariasis: Epidemiology, clinical manifestations, and diagnosis".)
Lymphangitis at non-peripheral sites — In addition to involvement of distal extremities, lymphangitis can also present at non-peripheral sites. Examples include:
●Mycobacterium tuberculosis can penetrate the ileocecal mucosa to reach the lymphoid tissue, which may generate an inflammatory response with lymphangitis.
●Filariasis can present with genital lymphatic involvement of the testes, scrotum, and epididymis as well as involvement of the renal lymphatics resulting in discharge of intestinal lymph into the urine (chyluria). (See "Lymphatic filariasis: Epidemiology, clinical manifestations, and diagnosis".)
Recurrent episodes — Recurrent episodes of lymphangitis should prompt evaluation for epidemiologic clues as outlined above. In addition, evaluation for predisposing conditions such as history of damage to lymphatic channels or developmental defects should be pursued. (See 'Pathophysiology' above.)
Noninfectious causes — Inflammation of the lymph vessels can occur in the setting of malignancy (known as neoplastic lymphangitis or lymphangitis carcinomatosa). Breast, lung, stomach, pancreas, rectal [27], and prostate cancers are the most common tumors that result in lymphangitis; lymphangitic spread of lymphoma has also been described [28,29].
Other underlying disease that can cause lymphangitis include Crohn disease (granulomatous intestinal lymphangitis) and sclerosing lymphangitis of the penis [30-32]. Lymphangitis has also been described following tuberculin skin testing [33] and following bites of arthropods, including spiders [34].
DIAGNOSIS — An etiological diagnosis of lymphangitis is made on the basis of epidemiology, clinical features, and laboratory analysis of clinical specimens.
Microbiologic investigations — Detailed information on diagnostic investigations for each etiology is discussed in detail separately. In general, diagnostic evaluation may include:
●Swab, aspirate, and/or biopsy of the primary site, nodule, or distal ulcer for histology and microscopy (including Gram, fungal, and acid-fast staining) as well as culture (including bacterial, fungal, and mycobacterial cultures). Cultures may require prolonged incubation for identification of Nocardia.
●Serology (eg, F. tularensis, Histoplasma).
●Blood film (eg, filaria).
●Molecular methods, including polymerase chain reaction (PCR) and 16S rRNA, have been used in the diagnosis of specific organisms that can cause lymphangitis but may be difficult to identify. Examples include Nocardia [35-37], Leishmania [38,39], and tularemia [40]. These methods are not generally available but may come into more common use.
Imaging — Imaging may be helpful for defining anatomic abnormalities such as dilated and tortuous lymphatics, although it is rarely useful for the diagnosis of infectious etiologies. Lymphangiography (using dye injection into the lymphatics) and lymphoscintigraphy (using intradermal technetium injection at distal site of affected limb) have been used to evaluate for lymphedema and/or lymphatic obstruction [41]. This may be useful if surgical management of lymphedema is a consideration [42]. (See "Clinical staging and conservative management of peripheral lymphedema".)
TREATMENT — Specific therapies for individual infections are discussed in detail separately. Some cases of nodular lymphangitis require surgical debridement. In the setting of lymphedema with significant lymphatic obstruction, surgical intervention may also be appropriate [42]. Pending diagnostic evaluation, empiric antibiotic therapy with activity against skin flora may be initiated as outlined in detail separately. (See "Acute cellulitis and erysipelas in adults: Treatment".)
SUMMARY AND RECOMMENDATIONS
●Lymphangitis is inflammation of lymphatic channels and most commonly develops after cutaneous inoculation of microorganisms into the lymphatic vessels through a skin wound or an abrasion or as a complication of a distal infection. (See 'Introduction' above.)
●Lymphangitis can occur in the setting of normal lymphatic channels with acute infection, damaged lymphatic channels, or anatomic abnormalities. Lymphatic damage and anatomic abnormalities can result in tissue protein and fluid accumulation, leading to nonpitting lymphedema with induration and predisposing to invasion of microorganisms. (See 'Pathophysiology' above.)
●The clinical manifestations of lymphangitis are variable and may be characterized by erythematous streaks with pain and rapid spread or by nodular swellings along the course of the lymphatic vessels. (See 'Clinical manifestations and microbiology' above.)
●The causes of acute lymphangitis include Streptococcus pyogenes, Staphylococcus aureus, and gram-negative organisms. Animal exposure can confer risk for lymphangitis due to Pasteurella, Erysipelothrix, and anthrax. Additional causes include herpes simplex virus, lymphogranuloma venereum, and rickettsiae. (See 'Acute lymphangitis' above.)
●The causes of nodular lymphangitis include Sporothrix schenckii, Nocardia (most often N. brasiliensis), Mycobacterium marinum, leishmaniasis, tularemia, Burkholderia pseudomallei, and systemic mycoses. (See 'Nodular lymphangitis' above.)
●Laboratory evaluation for lymphangitis may include swab, aspirate and/or biopsy of the primary site, nodule, or distal ulcer for histology, microscopy (including gram, fungal, and acid-fast staining), and culture (including bacterial, fungal, and mycobacterial cultures). (See 'Microbiologic investigations' above.)
●Treatment of lymphangitis includes targeted medical therapy. Some cases of nodular lymphangitis may require surgical debridement. In the setting of lymphedema with significant lymphatic obstruction, surgical intervention may also be appropriate. (See 'Treatment' above.)
