Larva Currens: Report of Seven Cases and Literature Review

ABSTRACT.

Strongyloidiasis is a frequent and often unrecognized parasitic disease because of the frequently asymptomatic nature and lack of sensitivity of diagnostic tests. Under conditions of immunosuppression (particularly systemic corticosteroid treatment), potentially fatal dissemination may occur. Thus, prevention and early diagnosis are important. Larva currens is a rare and pathognomonic cutaneous sign of strongyloidiasis, but is poorly described because of its unpredictable and fleeting occurrence. We report seven imported cases of larva currens seen in Paris between 1990 and 2020. We illustrate the clinical and biological features of this specific but uncommon sign of strongyloidiasis with clinical pictures. There were three males and four females, aged between 29 and 58 years. There were five migrants from endemic countries, one tourist and one expatriate. Digestive disorders were the main extracutaneous signs. All patients had eosinophilia above 0.5 G/L. All cases were confirmed by stool tests. All were cured with ivermectin. The rapidity and the short duration of the creeping eruption distinguish it from other parasitoses. Ivermectin is a treatment of choice. The key point is to think about preventing disseminated strongyloidiasis before giving corticosteroids not only among migrants but also among expatriates and tourists in endemic countries.

INTRODUCTION

Strongyloidiasis is a human intestinal nematodosis, caused by Strongyloides stercoralis. It affects around 600 million people worldwide according to the latest estimates in 2020, with the highest prevalence in tropical and intertropical regions in Southeast Asia, Africa, and South America as 76% of strongyloidiasis cases are found in these areas.¹

Larva currens is a rare and pathognomonic cutaneous manifestation of noninvasive strongyloidiasis. This dermatosis results from the subcutaneous passage of strongyloid larvae of S. stercoralis. It corresponds to the internal short cycle of self-infestation.² This name was given by Arthur and Shelley in 1958 to distinguish it from other causes of creeping dermatitis because of its rapid migration.³ It is a rare and poorly described manifestation as there are only 21 reported cases of larva currens in the literature.

The aim of this work is to report a series of seven patients seen during the last 30 years in a tropical diseases unit at the Pitié-Salpêtrière hospital in Paris, and to review the literature about larva currens.

MATERIALS AND METHODS

This is a retrospective observational study of all cases of larva currens observed in patients seen in the infectious and tropical diseases unit at the Pitié-Salpêtrière Hospital in Paris between January 1, 1990 and December 31, 2020.

Patients were included if they presented with a typical creeping dermatitis according to the literature.^3–5 Larva currens was defined as a linear or serpiginous, erythematous, papular, pruritic, recurrent subcutaneous trail, a few centimeters long, migratory with a rapid progression (5–15 cm/h), fleeting (a few hours), and preferentially localized around the buttocks, perineal area, or abdomen. The diagnosis of strongyloidiasis was always confirmed by a parasitological stool examination positive for S. stercoralis. Strongyloidiasis serology was not performed as it was not available before 2005 in the parasitology laboratory at the Pitié-Salpêtrière Hospital.

The following information was collected from the patients’ records: age, sex, country of origin, travel history, duration, cutaneous and extracutaneous signs, leukocyte count, eosinophil (percentage and count), total IgE level, treatment, and response to treatment. Hypereosinophilia was defined by an eosinophil count above 0.5 G/L. Cure was defined by the disappearance of clinical signs, normalization of eosinophil count, and a negative stool test at 3 months.

RESULTS

Cases are summarized inTable 1. Seven patients have been surveyed.

Table 1.

Clinical and biological presentation, treatment, and response to treatment in seven patients with larva currens

	1	2	3	4	5	6	7
Age (years old)	58	29	38	47	43	33	51
Year of diagnosis	2005	1991	1990	2000	1992	1991	1998
Sex	Woman	Woman	Man	Woman	Woman	Man	Man
History	Meningioma (2004)	Schistosomiasis (2001)	None	None	None	None	HIV (1997) Basedow’s disease (1984)
Country of origin	Cambodia, in France since 1966	Martinique, in metropolitan France since 1975	Brazil, in France since 1965	France	Tunisia between 0 and 9 years old	Congo, in France since 1981	France
Travel	Cambodia once a year since 1997	None	Saudi Arabia in 1979 Portugal once a year	Vietnam between August and November 1997	Ivory Coast between 9 and 11 years old Martinique between 11 and 17 years old French Guiana in 1992 (43 years old)	Congo every 2 years Brazil, Mexico	Living 6 to 8 months a year in Thailand since 1982. In France the rest of the time.
Cutaneous signs	Recurrent and fleeting CE on the buttocks	Recurrent, itchy, CE on different parts of the body (Figure 1)	Fleeting itchy CE, recurrent once or twice a year + anal pruritus since 1965	Pruritic lumbar CE in September 1997. Then chronic urticaria until July 2000	CE on the buttocks, thighs, knees, abdomen, for 15 minutes, 3–5 cm long	Several erythematous, pruritic, CE, 1–2 cm long and 0.5 cm wide, on abdomen, back and left arm (Figures 2 and 3)	Multiple, pruritic, papular erythematous CE, 1–5 cm long and 2–3 mm wide, on trunk and limbs (Figure 4)
Extracutaneous signs	Abdominal pain, diarrhea and weight loss (−10 kg)	None	Diarrhea and abdominal pain for 1 year	Diarrhea and abdominal pain	None	None	Diarrhea
Duration	Several years	20 years	25 years	3 years	20 years	5 years	Several years
Leukocyte counts	5.4 G/L in December 2004	7.8 G/L in April 1991	7.3 G/L in August 1990	6.1 G/L in June 2000	5.81 G/L	5.14 G/L	7.19 G/L
Eosinophil counts	1.84 G/L (30%) in December 2004	0.51 G/L (6.6%) in April 1991	0.67 G/L (9.2%) in August 1990	0.66 G/L (10.8%) in June 2000	0.61 G/L (10.5%)	0.82 G/L (16%)	1.80 G/L (25%)
Total IgE	ND	131 UI/mL (N < 250) in 1991	ND	30 UI/mL (N < 250)	ND	ND	ND
Stool test	Numerous rhabditoid larvae of S. stercoralis	Two rhabditoid larvae + one adult of S. stercoralis	Six rhabditoid larvae of S. stercoralis	Numerous rhabditoid larvae and some strongyloid larvae of S. stercoralis	One rhabditoid larvae of S. stercoralis	Numerous rhabditoid larvae of S. stercoralis	Rhabdoid larvae of S. stercoralis
Ivermectin (200 µg/kg)	Single dose	Two treatments one month apart*	Single dose	Single dose	Single dose	Two treatments 1 year apart†	Double dose
Outcome	No more digestive and skin disorders. Stool tests negative. Eosinophil counts: 0.16 G/L (5%)	Stool tests negative Eosinophil counts: 0.10 G/L (1.5%),	Stool tests negative Eosinophil counts: 0.06 G/L (1%)	Persistence of digestive disorders but no cutaneous signs Stool tests negative Eosinophil counts: 0.08 G/L (1.2%)	Skin signs disappeared Stool tests ND	Stool tests negative in after 1991 lost to follow-up after treatment in 1992	Skin signs disappeared Eosinophil counts: 0.43 G/L (6%) Stool test: ND

CE = creeping eruption; ND = not done.

^*Single half-dose ivermectin then double dose because CE relapsed 1 month after the 1srt Tt.

^†Single-dose ivermectin (1991) then double dose 2 days apart (1992) because of reinfection (travel in Congo) or failure.

There were three males and four females, aged from 29 to 58 at diagnosis (mean 43). There were five migrants who came from Cambodia, Congo, Tunisia, Martinique (French West Indies) and Brazil, one traveler to Vietnam, and one expatriate living in Thailand for 6–8 months each year. Larva currens was seen by clinicians in four patients (Figures 1–4). Two were seen with a single trail, one with three concomitant trails, and one with dozens of lesions on the trunk and limbs 3 days after the onset of systemic corticosteroid therapy for the treatment of hypoxemic pneumocystosis (without ivermectin previously). The three other patients consulted for recurrent creeping dermatitis, and the diagnosis of larva currens was raised by questioning them about the characteristics of the trail as they did not have clinical findings at the time of consultation. The main associated extracutaneous signs were digestive disorders found in four patients with abdominal pain (three patients) and diarrhea (four patients). The other three patients had no other associated signs. Larva currens has lasted for 3 to 25 years before diagnosis. It was not possible to evaluate retrospectively the periodicity of the larva currens occurrence. However, one patient declared two episodes per year, whereas another complained of many episodes per year.

Figure 1.

Patient n°2 with a serpiginous, erythematous, pruritic lesion on the back of the left thigh (↑).

Figure 2.

Patient n°6 with a serpiginous, erythematous trail, on the posterior side of the left arm.

Figure 3.

Patient n°6 with a papular, erythematous trail, on the left side of the back (↑).

Figure 4.

Patient n°7 with multiple serpiginous, pruritic, papular, erythematous lesions, 1–5 cm long and 2–3 mm wide, on the trunk.

Eosinophilia ranged from 0.514 G/L to 1.836 G/L (mean 0.987 G/L). All had a normal leukocyte count. Total IgE level performed in two patients was within normal range.

One of the patients (n°1) had a positive serology of Gnathostoma spinigerum with the Immunoblot technique (Dr. Paron Dekumyoy, Department of Helminthology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand) but the rapid migration and the transitory nature of the cutaneous trail ruled out the diagnosis of cutaneous gnathostomosis, which remains one of the main differential diagnoses of larva currens.

All were cured with ivermectin, four patients after receiving a single dose (200 µg/kg), and one after receiving a double dose (200 µg/kg/day 14 days apart). The two other patients were also cured with ivermectin but the outcome after a single dose is more difficult to evaluate because one (patient 2) relapsed after receiving an inadequate dosage, and the other (patient 6) after a travel in Congo (Table 1).

DISCUSSION

This series of seven cases of larva currens is unique to date as it was collected over a 30-year period. Indeed, despite the frequency of this specific manifestation in strongyloidiasis it is rarely seen by clinicians. Our series illustrates the clinical and biological features of this form of strongyloidiasis.

The fleeting and the unpredictable occurrence of larva currens makes the illustration of this disease very informative, as most patients are not seen with the cutaneous trail of larva currens at the time of consultation because the creeping eruption lasts no more than a few hours. It is noteworthy that one of our patients (patient 7) developed an isolated diffuse cutaneous form of larva currens after the introduction of systemic corticosteroid therapy, that has been described only twice up to now.^6,7

Obviously, larva currens is a rarely seen manifestation of strongyloidiasis as it took 30 years to include seven patients, all observed in a tropical disease unit with some experience in tropical dermatology. Only 21 cases have been described in the literature so far. The largest series in the literature included four patients but did not include descriptions of geographical origin and travel, treatment and response to treatment, nor illustrative photographs of larva currens for any of the patients.⁸

However, larva currens was frequently reported among former prisoners of war (POW) sent to forced labor on the Siam-Burma railways during World War II. Indeed, in a series of 2,072 former British POW, 70% of the 172 patients diagnosed with strongyloidiasis complained of larva currens.⁹ In another series, larva currens was self-declared by 30% (13/44) of the Australian POW diagnosed with strongyloidiasis.¹⁰ This high frequency is not found outside of POWs in Southeast Asia working on the Siam-Burma railways. For example, no case of larva currens was found in a study of 78 cases of creeping dermatitis recorded between 2008 and 2013 in our department,¹¹ neither among the 70 cases of strongyloidiasis collected in an Iranian series,¹² nor among the 63 autochthonous cases of strongyloidiasis diagnosed in the Midi-Pyrenees Region in France.¹³

In our series, there were five migrants, one tourist, and one expatriate which show the large spectrum of people sharing at-risk behaviors such as walking barefoot. Our five migrants were from Cambodia, Congo, Tunisia, Martinique (French West Indies), and Brazil, which is not surprising as South/Central America, Africa, and Southeast Asia are endemic regions for strongyloidiasis with a prevalence over 10%.^1,14

In nonendemic countries, some studies evaluated the prevalence of strongyloidiasis among migrants and travelers. Strongyloidiasis mainly concerns migrants from Southeast Asia, sub-Saharan Africa, and South/Central America with a prevalence estimated at 17.3%, 14.6%, and 11.4%, respectively, in a systematic review and meta-analysis of strongyloidiasis.¹⁵ At the opposite end of the spectrum, the prevalence among expatriates and travelers is less than 1%. A Dutch prospective study involving 1,207 travelers seen in predeparture consultations, then 2 and 6 weeks after their return, found a seroconversion for strongyloidiasis in three travelers (0.25%), all returning from Asia.¹⁶ A Canadian study done between 1981 and 1987 showed only seven cases (0.4%) of strongyloidiasis among 1,605 expatriates.¹⁷ Another Canadian study performed between 1997 and 2003 showed nine cases (2.3%) of strongyloidiasis among 390 migrants and 13 cases (0.7%) of strongyloidiasis among 1,896 tourists.¹⁸

In our study, the duration between the onset of signs and the diagnosis varied from 3 to 25 years. Strongyloidiasis is a lifelong disease because of its capacity for self-infestation, as illustrated by the case of British soldiers who were POW in Thailand on the Siam-Burma railway and who were diagnosed with strongyloidiasis a mean of 37 years after their repatriation.⁹ Moreover, in 2011, the case of an 83-year-old man diagnosed with strongyloidiasis was reported 75 years after a childhood trip to Vietnam.¹⁹

Larva currens is a cause of creeping dermatitis, but the rapidity of its progression (5–15 cm/h) and the fleeting nature of the eruption (a few hours) distinguish it from other parasitoses.^3,20 Other parasitic causes of creeping dermatitis include hookworm-related cutaneous larva migrans, which is the most common cause¹¹; gnathostomosis²¹; loiasis²²; rampant myiasis resulting from Gasterophilus spp. and Hypoderma spp.,²³ Spirurina infection, mainly found in Japan²⁴; and fasciolosis.²⁵ Pili migrans is another non-parasitic cause of creeping dermatitis.²⁶

The other skin manifestations of strongyloidiasis are varied.⁴ During the penetration phase, localized edema, papules, and petechiae are observed at the point of penetration of S. stercoralis, which may persist for several weeks, as shown by the experiments on self-inoculation of S. stercoralis larvae by Dr. Tanaka,²⁷ Dr. Sandground, and Dr. Desportes.²⁸ Acute urticaria is more characteristic of the invasive phase as illustrated by the case of an Italian couple. Seven days after returning from Thailand, both developed acute urticaria associated with fever, coughing, and asthenia accompanied by eosinophilia greater than 5 G/L and a parasitological examination of the stool positive for S. stercoralis.²⁹ However, urticaria has also been described during the chronic phase.^30,31 Periumbilical purpura (thumbprint sign) is pathognomonic of invasive strongyloidiasis.³²

One of our cases (n°7), an AIDS patient, developed profuse cutaneous strongyloidiasis with multiple lesions of larva currens on the trunk and limbs, without any other sign of extracutaneous invasion, after being prescribed systemic corticosteroids without preexisting presumptive antistrongyloidiasis treatment as it was not advised at that time in nonmigrant persons (1998). The patient improved very quickly after double dose ivermectin. This clinical form therefore has a better prognosis than severe strongyloidiasis (hyperinfectious syndrome or disseminated strongyloidiasis) which has a high mortality rate of 62.7%,³³ but which can reach 87% among those who develop a secondary bacterial infection.³⁴ This is a rare picture and only two similar cases have been described in the literature in immunocompromised patients.^6,7

Current diagnostic methods still lack sensitivity. Hypereosinophilia is inconstant because it fluctuates,³⁵ but is more frequent than in other intestinal parasitic infections.³⁶ In our case series, hypereosinophilia was present at the time of diagnosis, in all patients when considering the threshold at 0.5 G/L, and in three out of seven patients when considering the threshold at 0.7 G/L. The standard parasitological examination of the stool has a sensitivity of 20–30%,³⁷ but this reaches 100% when the examination is repeated more than seven times because the excretion of parasites in the stool is variable depending on the day.³⁵ The sensitivity of the parasitological stool examination is also increased using the Baermann method and agar plate culture to 72% and 89%, respectively.³⁸ Serology has a sensitivity between 75% and 100% depending on the technique,³⁹ whereas polymerase chain reaction (PCR) offers no advantage over parasitological examination of stool.⁴⁰ None of our patients had a serology because this technique was not available at that time.

Strongyloidiasis is asymptomatic in more than 50% of cases. However, it can be lethal in case of disseminated form in immunocompromised people, especially when receiving systemic corticosteroid therapy. Wikman-Jorgensen et al. have shown that preventive treatment of immunosuppressed migrants from endemic areas is the most cost effective.⁴¹ Preventive treatment before immunosuppression, especially before systemic corticosteroid therapy should also be given to travelers, as cases of strongyloidiasis are increasing among tourists in endemic areas.⁴²

The treatment of strongyloidiasis is currently based on ivermectin, 200 µg/kg in a single dose.⁴³ Three cases of larva currens have been successfully treated with ivermectin, all included in this series.⁴⁴ Buonfrate et al. showed that single-dose ivermectin was as effective as quadruple-dose ivermectin (200 µg/kg/day on days 1, 2, 15, and 16).⁴⁵ Several randomized trials have shown that single-dose ivermectin is as effective as thiabendazole but much better tolerated,⁴⁶ and that single-dose (150–200 µg/kg) ivermectin is more effective than 7-days long treatment with albendazole.⁴⁷ The effectiveness of the treatment can be assessed by the negativation of parasitological stool examinations with concentration techniques,³⁸ or by a reduction of the serological titer.⁴⁸

In conclusion, we were able to observe seven cases of larva currens within 30 years. Given the fleeting nature of the disease, we were lucky to catch the clinical presentation on the day of the consultation in four patients. The key point related to strongyloidiasis is to think about preventing disseminated strongyloidiasis before giving corticosteroids not only among migrants but also among expatriates, or even tourists in endemic countries.